JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Liposome encapsulated Disulfiram inhibits NF?B pathway and targets breast cancer stem cells in vitro and in vivo.
Oncotarget
PUBLISHED: 10-04-2014
Show Abstract
Hide Abstract
Breast cancer stem cells (BCSCs) are pan-resistant to different anticancer agents and responsible for cancer relapse. Disulfiram (DS), an antialcoholism drug, targets CSCs and reverses pan-chemoresistance. The anticancer application of DS is limited by its very short half-life in the bloodstream. This prompted us to develop a liposome-encapsulated DS (Lipo-DS) and examine its anticancer effect and mechanisms in vitro and in vivo. The relationship between hypoxia and CSCs was examined by in vitro comparison of BC cells cultured in spheroid and hypoxic conditions. To determine the importance of NF?B activation in bridging hypoxia and CSC-related pan-resistance, the CSC characters and drug sensitivity in BC cell lines were observed in NF?B p65 transfected cell lines. The effect of Lipo-DS on the NF?B pathway, CSCs and chemosensitivity was investigated in vitro and in vivo. The spheroid cultured BC cells manifested CSC characteristics and pan-resistance to anticancer drugs. This was related to the hypoxic condition in the spheres. Hypoxia induced activation of NF?B and chemoresistance. Transfection of BC cells with NF?B p65 also induced CSC characters and pan-resistance. Lipo-DS blocked NF?B activation and specifically targeted CSCs in vitro. Lipo-DS also targeted the CSC population in vivo and showed very strong anticancer efficacy. Mice tolerated the treatment very well and no significant in vivo nonspecific toxicity was observed. Hypoxia induced NF?B activation is responsible for stemness and chemoresistance in BCSCs. Lipo-DS targets NF?B pathway and CSCs. Further study may translate DS into cancer therapeutics.
Related JoVE Video
Extruded Soluplus/SIM as an oral delivery system: characterization, interactions, in vitro and in vivo evaluations.
Drug Deliv
PUBLISHED: 10-01-2014
Show Abstract
Hide Abstract
Abstract The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg. The drug was proved to be miscible with Soluplus by calculation and measurements. The solubility, dissolution, thermal characteristics, interactions and physical stability of the SIM/Soluplus SDs were investigated. The crystal state of simvastatin in the SD was found to change from crystalline to amorphous form during the HME process and also hydrogen bonds were observed between SIM and the extruded Soluplus. The phase solubility showed the solubilization effect of Soluplus was strong and spontaneous. The equilibrium solubility illustrated that Soluplus/SIM SDs gained much higher solubility than its corresponding physical mixtures (PMs). Both of the dissolution profiles and in-vivo performance showed that the SIM/Soluplus SD obtained a marked enhancement, compared with the PM. There was a little change in the SIM/Soluplus SD during a 3-month storage period (40?°C, 75%), indicating the good physicochemical stability. The extruded Soluplus system prepared by HME is a good alternative for the water-insoluble SIM to improve the stability and bioavailability.
Related JoVE Video
In Vivo Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles.
IEEE Trans Med Imaging
PUBLISHED: 09-30-2014
Show Abstract
Hide Abstract
The structure of microvasculature cannot be resolved using standard clinical ultrasound (US) imaging frequencies due to the fundamental diffraction limit of US waves. In this work, we use a standard clinical US system to perform in vivo sub-diffraction imaging on a CD1, female mouse aged 8 weeks by localizing isolated US signals from bubbles flowing within the ear microvasculature, and compare our results to optical microscopy. Furthermore, we develop a new technique to map blood velocity at super-resolution by tracking individual bubbles through the vasculature. Resolution is improved from a measured lateral and axial resolution of 112 ?m and 94 ?m respectively in original US data, to super-resolved images of microvasculature where vessel features as fine as 19 ?m are clearly visualized. Velocity maps clearly distinguish opposing flow direction and separated speed distributions in adjacent vessels, thereby enabling further differentiation between vessels otherwise not spatially separated in the image. This technique overcomes the diffraction limit to provide a non-invasive means of imaging the microvasculature at super-resolution, to depths of many centimeters. In the future, this method could noninvasively image pathological or therapeutic changes in the microvasculature at centimeter depths in vivo.
Related JoVE Video
Ultra-bright alkylated graphene quantum dots.
Nanoscale
PUBLISHED: 09-06-2014
Show Abstract
Hide Abstract
Highly efficient and stable photoluminescence (PL) are urgently desired for graphene quantum dots (GQDs) to facilitate their prospective applications as optical materials. Here, we report the facile and straightforward synthesis of alkylated graphene quantum dots (AGQDs) via the solvothermal reaction of propagatively alkylated graphene sheets (PAGenes). In contrast to most GQDs reported so far, the synthesized AGQDs process pH-independent and ultra-bright PL with a relative quantum yield of up to 65%. Structural and chemical composition characterization demonstrated that the synthesized AGQDs are nearly oxygen-defect-free with alkyl groups decorated on edges and basal plane, which may contribute to their greatly improved pH tolerance and high quantum efficiency. The photocatalytic performance of AGQDs-P25 nanocomposites was evaluated by the degradation of Rhodamine B under visible light. The photocatalytic rate is ca. 5.9 times higher than that of pure P25, indicating that AGQDs could harness the visible spectrum of sunlight for energy conversion or environmental therapy.
Related JoVE Video
CUL4B promotes proliferation and inhibits apoptosis of human osteosarcoma cells.
Oncol. Rep.
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
Cullin 4B (CUL4B) is a component of the Cullin4B-Ring E3 ligase complex (CRL4B) that functions in proteolysis and is implicated in tumorigenesis. Here, we report that CUL4B is associated with tumorigenesis by promoting proliferation and inhibiting apoptosis of human osteosarcoma cells. We performed RNA interference (RNAi) with a lentiviral vector system to silence the CUL4B gene using osteosarcoma SAOS-2 cells. The negative control included the normal target cells infected with the negative control virus whereas the knockdown cells included the normal target cells transfected with the RNAi target virus. We assessed the inhibition resulting from the decreased expression of the CUL4B gene on the proliferation rate of SAOS-2 cells, and also evaluated the cell cycle distribution, apoptosis and clonability. Compared with the negative control, the CUL4B gene expression was significantly inhibited in the SAOS-2 cells at the mRNA and protein levels in the knockdown group (P<0.01). Furthermore, in the knockdown group, the cell proliferation rate and clonability were also significantly inhibited (P<0.01). The apoptosis rate increased significantly (P<0.05). A significant decrease in the number of cells in the G1 phase (P<0.01) and significant increases in the S (P<0.01) and G2 phases (P<0.05) were observed. The silencing of CUL4B gene expression can effectively inhibit osteosarcoma cell proliferation and induce apoptosis. These findings may provide a novel biomarker for the treatment of osteosarcoma.
Related JoVE Video
Theoretical Prediction of a Phase Diagram for Solid Dispersions.
Pharm. Res.
PUBLISHED: 08-28-2014
Show Abstract
Hide Abstract
To predict the temperature-composition phase diagram of solid dispersions (SDs) through theoretical approaches using cinnarizine-Soluplus(®) SD as a model system and evaluate the predicted results.
Related JoVE Video
Increased dissolution of disulfiram by dry milling with silica nanoparticles.
Drug Dev Ind Pharm
PUBLISHED: 08-18-2014
Show Abstract
Hide Abstract
Abstract The purpose of this study was to find a suitable method to increase the dissolution of disulfiram (DSF) which is easily decomposed. The dissolution of DSF within 1?h was significantly increased from 37% to >90% by co-milling with Aerosil® 200 pharm (Aerosil) and the increased dissolution remained stable during long-term storage while there was no significant degradation of DSF. By monitoring the changes in particle size of the grinding mixture, a mosaic DSF-in-Aerosil structure was demonstrated. The core size of the mosaic DSF/Aerosil system was 3.625?µm. The particle size of DSF was reduced from 20.75?µm to ?200?nm and the size of the mosaic DSF/Aerosil system (3.625?7.956?µm) increased on increasing the drug-loading content. Differential scanning calorimetry and X-ray powder diffraction analysis confirmed the largely amorphous state of DSF in the mosaic drug/carrier system. Fourier transform infrared spectroscopy confirmed the presence of hydrogen bonding between DSF and Aerosil. Scanning electron microscopy and transmission electron microscopy verified the DSF-in-Aerosil relationship in the particle size determination at different size levels. The possible mechanisms of dry milling included the hypothesis that during impact and collision, DSF particles melted into the surface of Aerosil turning them into an amorphous state or they became inlayed into the interspaces of the Aerosil structure with a much smaller size.
Related JoVE Video
Enhanced brain delivery of lamotrigine with Pluronic(®) P123-based nanocarrier.
Int J Nanomedicine
PUBLISHED: 08-16-2014
Show Abstract
Hide Abstract
P-glycoprotein (P-gp) mediated drug efflux across the blood-brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG).
Related JoVE Video
Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG-poly(glutamic acid)2 copolymers via hydrazone linkers.
Molecules
PUBLISHED: 08-11-2014
Show Abstract
Hide Abstract
In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.
Related JoVE Video
Application of an LC-MS/MS method to the pharmacokinetics of TM-2, a potential antitumour agent, in rats.
Drug Test Anal
PUBLISHED: 07-14-2014
Show Abstract
Hide Abstract
TM-2 is a novel semi-synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of TM-2 in rat plasma. The biological samples were extracted with methyl tert-butyl ether and separated on a C18 column (50?mm?×?2.1?mm, 1.7?µm) using a mobile phase consisting of acetonitrile and 2?mM ammonium acetate. The standard curves were linear over the range 5-1000?ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from -1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM-2 to rats. The pharmacokinetics of TM-2 in rats were characterized by a large volume of distribution and a long half-life of elimination after single dose (4, 8, and 16?mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM-2. Copyright © 2014 John Wiley & Sons, Ltd.
Related JoVE Video
Fabrication of photo-crosslinked chitosan- gelatin scaffold in sodium alginate hydrogel for chondrocyte culture.
Biomed Mater Eng
PUBLISHED: 06-24-2014
Show Abstract
Hide Abstract
Photo-crosslinked chitosan-gelatin scaffolds were fabricated and applied for chondrocyte culture in vitro. Photocurable methacryloyl chitosan was synthesized and characterized by FTIR and 1H NMR, respectively. Microstructure and mechanical properties of the chitosan-gelatin scaffold treated with or without EDC as crosslinking agent were analyzed by scanning electronic microscopy (SEM), compression and viscoelastic measurement. It is demonstrated that EDC-treated chitosan-gelatin scaffold possesses better porous structure and improved mechanical properties. Photo-crosslinked chitosan-gelatin scaffold could be further integrated in sodium alginate hydrogel using calcium chloride to support proliferation of chondrocytes for over 21 days and maintain spherical phenotype, as evaluated by AlamarBlue assay and SEM, respectively, implying that the chitosan-gelatin-hydrogel system exhibits great cyto-biocompatibility. Results of this study show that photo-crosslinked chitosan-gelatin scaffold in sodium alginate hydrogel is suited as a scaffold candidate for cartilage tissue engineering.
Related JoVE Video
TMDB: A literature-curated database for small molecular compounds found from tea.
BMC Plant Biol.
PUBLISHED: 06-05-2014
Show Abstract
Hide Abstract
Tea is one of the most consumed beverages worldwide. The healthy effects of tea are attributed to a wealthy of different chemical components from tea. Thousands of studies on the chemical constituents of tea had been reported. However, data from these individual reports have not been collected into a single database. The lack of a curated database of related information limits research in this field, and thus a cohesive database system should necessarily be constructed for data deposit and further application.
Related JoVE Video
[Management of moderate to severe pediatric concealed penis in children by Devine's technique via incision between the penis and scrotum].
Zhonghua Nan Ke Xue
PUBLISHED: 05-31-2014
Show Abstract
Hide Abstract
To search for a simple and effective surgical approach to the management of moderate to severe pediatric concealed penis in children.
Related JoVE Video
Hydroxyethyl starch-10-hydroxy camptothecin conjugate: synthesis, pharmacokinetics, cytotoxicity and pharmacodynamics research.
Drug Deliv
PUBLISHED: 05-17-2014
Show Abstract
Hide Abstract
Abstract 10-hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by poor water solubility, low lactone stability, short plasma half-life and dose-limiting toxicity. In this study, 10-HCPT-hydroxyethyl starch (HES) conjugate was prepared to overcome these limits of 10-HCPT. The solubility of 10-HCPT conjugate was 0.72?mg/ml, about 100 times to free 10-HCPT. The 10-HCPT conjugate showed good sustained release effect in phosphate-buffered saline (PBS), rat plasma and liver homogenate. Meanwhile, 10-HCPT-HES conjugate achieved much lower IC50 and higher cytotoxicity effects than the free 10-HCPT on Hep-3B liver cancer cells. The pharmacokinetics results of 10-HCPT-HES conjugate demonstrated that the biological half-life of 10-HCPT was increased from 10?min to 4.38?h and the bioavailability was 40 times higher than the commercial 10-HCPT injection. The pharmacodynamics results indicated that 10-HCPT-HES conjugate had a better antitumor efficiency against nude mouse with Hep-3B tumor than the commercial 10-HCPT injection, and the inhibition ratio of tumor was 83.9 and 27.8%, respectively, at the same administration dosage. These findings suggest that 10-HCPT-HES conjugate is a promising drug delivery system providing improved long circulating effect, greater stability and better antitumor effect.
Related JoVE Video
A comparison of the effect of temperature and moisture on the solid dispersions: Aging and crystallization.
Int J Pharm
PUBLISHED: 04-30-2014
Show Abstract
Hide Abstract
The purpose of this work was to compare the effect of temperature and relative humidity (RH) on the physical stability and dissolution of solid dispersions. Cinnarizine-Soluplus(®) solid dispersions (SDs) at three different drug loadings (10, 20 and 35wt%) were prepared by hot melt extrusion and exposed to stress conditions: high temperatures (40 and 60°C), high relative humidities (75% and 94% RH) and accelerated conditions (40°C/75% RH) for 30 days, or stored at 25°C for up to 5 months. Changes in solid state and dissolution of SDs were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and dissolution testing. For samples under stress conditions, the results showed a reduced dissolution and a recrystallization of the drug with an increased crystallinity in the order of 40°C/75% RH, >60°C/0% RH, >25°C/94% RH, >40°C/0% RH, >25°C/75% RH. For samples stored at 25°C, nonlinear physical aging was observed and the dissolution also decreased although the SDs were still amorphous. The results indicated that temperature and humidity seemed to have comparable effects on the crystallization of cinnarizine-Soluplus(®) SDs. It is not reasonable to regard recrystallization as a sign of reduced dissolution, and glass transition temperature (Tg) may be a good indicator of the changes in dissolution.
Related JoVE Video
Hydrothermal synthesis of nanocrystalline NaX zeolite at room temperature.
J Nanosci Nanotechnol
PUBLISHED: 04-25-2014
Show Abstract
Hide Abstract
NaX zeolites were prepared by hydrothermal synthesis under room-temperature conditions. Some influence parameters such as crystallization time, Al2O3/SiO2, Na2O/SiO2 and H2O/SiO2 molar ratios on the crystalline end products were studied, the products were characterized by XRD, SEM, TEM, particle size analysis and N2 adsorption-desorption techniques. The results indicated that although 28 days product was fully crystalline according to the XRD investigation, the crystals were able to continue to grow. The TEM revealed that the samples were composed of highly crystalline NaX zeolite nanocrystals with the average size of around 30 nm. Long crystallization time favored the aggregation of individual nanocrystals, which led to the formation of large congregated agglomerates. Furthermore, mild alkalinity circumstance was favorable for the crystallization of FAU zeolite. However, higher water quantity resulted in the formation of larger steady congregated agglomerates. The samples obtained with H2O/SiO2 molar ratios of 100, 150, 250, 300 and 400 showed the mean particle sizes of 42, 108, 359, 551 and 962 nm, with the particle size distribution ranges of 30-63, 62-140, 215-602, 345-746 and 498-1395 nm, respectively.
Related JoVE Video
Thiolated eudragit-based nanoparticles for oral insulin delivery: preparation, characterization, and evaluation using intestinal epithelial cells in vitro.
Macromol Biosci
PUBLISHED: 04-16-2014
Show Abstract
Hide Abstract
This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed of thiolated Eudragit L100 (Eul-cys) and reduced glutathione (GSH) as potential nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an average particle size of nearly 200-300?nm are prepared. The insulin release from Eul-cys/GSH and Eul-cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease the release rate of insulin. Eul-cys in combination with GSH or sodium caprate (SC) is evaluated for its permeation enhancing effect of FITC-insulin using the Caco-2 monolayer and Caco-2/HT29-MTX co-cultured cells models. SC results in greater permeation enhancement compared to GSH. However, GSH proves to be less toxic. Paracellular transport of insulin represents the main mechanism by which the NPs facilitate insulin permeation through the intestinal epithelium, whereas a number of NPs are also taken up by the cells and release insulin within the cells.
Related JoVE Video
A combined bottom-up/top-down approach to prepare a sterile injectable nanosuspension.
Int J Pharm
PUBLISHED: 04-15-2014
Show Abstract
Hide Abstract
To prepare a uniform nanosuspension of strongly hydrophobic riboflavin laurate (RFL) allowing sterile filtration, physical modification (bottom-up) was combined with high-pressure homogenization (top-down) method. Unlike other bottom-up approaches, physical modification with surfactants (TPGS and PL-100) by lyophilization controlled crystallization and compensated for the poor wettability of RFL. On one hand, crystal growth and aggregation during freezing was restricted by a stabilizer-layer adsorbed on the drug surface by hydrophobic interaction. On the other hand, subsequent crystallization of drug in the sublimation process was limited to the interstitial spaces between solvent crystals. After lyophilization, modified drug with a smaller particle size and better wettability was obtained. When adding surfactant solution, water molecules passed between the hydrophilic groups of surface active molecules and activated the polymer chains allowing them to stretch into water. The coarse suspension was crushed into a nanosuspension (MP=162 nm) by high-pressure homogenization. For long term stability, lyophilization was applied again to solidify the nanosuspension (sorbitol as cryoprotectant). A slight crystal growth to about 600 nm was obtained to allow slow release for a sustained effect after muscular administration. Moreover, no paw-licking responses and very slight muscular inflammation demonstrated the excellent biocompatibility of this long-acting RFL injection.
Related JoVE Video
Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.
Int J Pharm
PUBLISHED: 04-05-2014
Show Abstract
Hide Abstract
This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma.
Related JoVE Video
Tracking shear waves in turbid medium by light: theory, simulation, and experiment.
Opt Lett
PUBLISHED: 04-03-2014
Show Abstract
Hide Abstract
Shear wave propagation provides rich information for material mechanical characterization, including elasticity and viscosity. This Letter reports tracking of shear wave propagation in turbid media by laser-speckle-contrast analysis. The theory is described, and a Monte Carlo simulation of light shear wave interaction was developed. Simulation and experiments on tissue-mimicking phantoms agree well and show tracking of shear wave at the phantom surface and at depth as well as multiple shear waves interacting within the object. The relationship between speckle contrast value and shear wave amplitude is also investigated.
Related JoVE Video
The use of portable 2D echocardiography and 'frame-based' bubble counting as a tool to evaluate diving decompression stress.
Diving Hyperb Med
PUBLISHED: 04-02-2014
Show Abstract
Hide Abstract
'Decompression stress' is commonly evaluated by scoring circulating bubble numbers post dive using Doppler or cardiac echography. This information may be used to develop safer decompression algorithms, assuming that the lower the numbers of venous gas emboli (VGE) observed post dive, the lower the statistical risk of decompression sickness (DCS). Current echocardiographic evaluation of VGE, using the Eftedal and Brubakk method, has some disadvantages as it is less well suited for large-scale evaluation of recreational diving profiles. We propose and validate a new 'frame-based' VGE-counting method which offers a continuous scale of measurement.
Related JoVE Video
A highly stable norcantharidin loaded lipid microspheres: preparation, biodistribution and targeting evaluation.
Int J Pharm
PUBLISHED: 03-28-2014
Show Abstract
Hide Abstract
The purpose of this study was to prepare norcantharidin (NCTD)-loaded lipid microspheres (LMs) with a high encapsulation efficiency (EE) and stability during sterilization. The NCTD-phospholipid complex (NPC) was produced and characterized to increase the lipophilic properties of NCTD and a novel concentrated homogenization method was applied for the preparation of LMs. The results of the UV, DSC and IR investigations confirmed the formation of NPC. The oil-water partition coefficient (log P) of NPC was significantly increased with a value of -1.34 ± 0.06 at pH 7.4, nearly 224 times higher than that of NCTD. A concentrated emulsion was prepared based on a homogenization method and then diluted with water. After optimization of the NPC formation and emulsion preparation process, the EE was dramatically increased from 21.6% to 84.6%, and a highly sterilization stability was achieved with only a minor change in particle size from 168.2 ± 39.4 nm to 173.4 ± 43.5 nm. The tissue distribution of NPCLM was measured after intravenous administration to rats of a dose of 3.9 mg/kg with NCTD injection (NI) as the reference. Considerably increased concentrations of NCTD in the liver, spleen and lung were detected with NPCLM and the values were 1.67, 1.49 and 1.06 times higher than in the NI group, respectively while, in the kidney, the concentration was slightly reduced 0.96-fold. Overall, based on these techniques, this NPCLM with an improved EE and stability offers great promise in clinical applications and industrial-scale production along with a potentially increased targeting effect on the liver and reduced toxicity in the kidney.
Related JoVE Video
Impact of electrolytes on double emulsion systems (W/O/W) stabilized by an amphiphilic block copolymer.
Colloids Surf B Biointerfaces
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
In this work, the block copolypeptide surfactant, poly(l-lysine·HBr)40-b-poly(racemic-leucine)20, was synthesized and characterized, then used to build water-in-oil-in-water (W/O/W) double emulsions. Double emulsions are usually prepared by a two-step emulsification process and commonly stabilized using a combination of hydrophilic and hydrophobic surfactants. Herein, we report a one-step phase inversion process to produce water-in-oil-in-water (W/O/W) double emulsions stabilized by a synthetic diblock copolymer and electrolyte. It was found that the O/W ratio and the type of electrolyte had a marked effect on the formation and type of the double emulsions. Moreover, double emulsions containing an NaCl isotonic solution were stable for at least two months, whereas those using glucose as a substitute for NaCl showed a clear compartmental change. The mechanism behind this was related to the electrostatic interaction between the anion of the electrolyte and the cation of the polylysine residues, which affected the HLB value and curvature. This novel finding is very interesting in terms of both scientific research and practical applications.
Related JoVE Video
Influence of potential inhalation carriers on stability of thymopentin in rat bronchoalveolar lavage fluid.
Drug Deliv
PUBLISHED: 03-10-2014
Show Abstract
Hide Abstract
In the present study, the stability of thymopentin (TP5) in bronchoalveolar lavage fluid (BALF) in presence of potential excipients in inhalation formulation was investigated. The content of TP5 was determined using HPLC method. Commonly used bulking agent, dispersibility enhancers and absorption enhancers in inhalation were investigated with respect to the stability of TP5 in BALF. Finally, the stability of TP5 in two inhalation formulations based on the screening experiments was tested in BALF. The results showed that TP5 alone degraded very rapidly in BALF and zero-order enzymatic reaction with a half-life of t0.5?=?49.20?min was observed using 10 times diluted BALF. Among the amino acids examined, leucine and phenylalanine effectively inhibited the enzymolysis of TP5 with prolonged half-life of 112.7?min and 136.2?min, respectively. Nevertheless, slight but insignificant inhibition effect was witnessed for tyrosine, aspartic acid, and lysine; and negligible prevention on the degradation process of TP5 were found for lactose and mannitol. Regarding chitosan, irrespective with molecular weight, the formation of chitosan-TP5 complex improved the stability of TP5 with prolonged t0.5 by 1.8 times. However, along with the improved stability of TP5 in spray-dried chitosan microspheres, the content of TP5 in formulations was reduced to about 75% during preparation process. Thus, leucine was proved to be a prior candidate for inhalation formulation of TP5. Consequently, the results indicate the potential of leucine as carrier for pulmonary delivery of TP5 serving as both stabilizer and dispersibility enhancer.
Related JoVE Video
Novel hydrophobin-coated docetaxel nanoparticles for intravenous delivery: in vitro characteristics and in vivo performance.
Eur J Pharm Sci
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
Novel hydrophobin (H star Protein® B, HPB)-coated docetaxel (DTX) nanoparticles were designed for intravenous delivery. DTX-HPB nanoparticles (DTX-HPB-NPs) were prepared using a nanoprecipitation-ultrasonication technique. The physicochemical properties in terms of particle size, size distribution, zeta potential, morphology, crystalline state of the drug, in vitro release and plasma stability were evaluated. To investigate the drug-hydrophobin interaction, FTIR analysis was carried out. The pharmacokinetics of DTX-HPB-NPs and Taxotere were compared after i.v. administration to rats. The optimized formulations have a high drug loading (>25%) and nanoparticle yield (>93%), small particle size with a narrow distribution, and exhibit delayed release. X-ray diffraction (XRD) demonstrated that the drug is present in a crystalline state. FTIR analysis suggested that the interaction of DTX and HPB involved hydrogen bonding. In vitro hemolysis study confirmed the safety of these nanoparticles. In plasma, DTX-HPB nanoparticles exhibited a significantly enhanced Cmax (1300.618±405.045 ng/mL vs 453.174±164.437 ng/mL, p<0.05), and AUC0-t (409.602±70.267 vs 314.924±57.426 ?g/Lh, p<0.05), and a significantly reduced volume of distribution (36.635±15.189 vs 95.199±40.972 L/kg, p<0.05) compared with the Taxotere. These results demonstrated that hydrophobin has the potential to be used as a novel biocompatible biomaterial for drug delivery.
Related JoVE Video
Dynamics of targeted microbubble adhesion under pulsatile compared with steady flow.
Ultrasound Med Biol
PUBLISHED: 03-05-2014
Show Abstract
Hide Abstract
Hemodynamic flow variations at low fluid shear stress are thought to play a critical role in local atherosclerotic plaque initiation and development and to affect plaque instability. Targeted microbubbles are being developed as intravascular agents for identifying atherosclerotic lesions using ultrasound. How variations in local hydrodynamic flow influence the adhesiveness of targeted microbubbles is not well understood. We postulated that rates of targeted microbubble binding and accumulation differ when subjected to steady flow (SF) as compared with oscillatory or pulsatile flow (PF), because PF imposes non-uniform blood rheology and periodic acceleration and deceleration of blood velocity, when compared with SF. We assessed the binding rates of targeted microbubbles in seven randomly assigned PF and seven matched SF replicate runs at low (<1 Pa) and intermediate (?1 and <2.5 Pa) wall shear stress (WSS) by drawing 4.8 × 10(6) microbubbles mL(-1) over streptavidin-coated substrates, immobilized within a parallel plate flow chamber at a calculated density of 81 binding sites ?m(-2). Selective binding and accumulation of targeted microbubbles was recorded in a single field of view using real-time video microscopy. Microbubble accumulation was modeled to obtain flow-mediated microbubble binding kinetics (amplitude, A, and rate constant, k). PF elicited higher microbubble accumulation rates, in comparison to SF. The rates of microbubble accumulation differed significantly between PF and SF (p < 0.05) at intermediate WSS but not at low WSS (p > 0.05). The rate of microbubble accumulation decreased as WSS increased.
Related JoVE Video
Development of a rapid and sensitive UPLC-MS/MS assay for the determination of TM-2 in beagle dog plasma and its application to a pharmacokinetic study.
Biomed. Chromatogr.
PUBLISHED: 02-23-2014
Show Abstract
Hide Abstract
A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50?×?2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 812.39???551.35 for TM-2 and 836.36???555.26 for IS, respectively. The method was linear for TM-2 (r?=?0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively. Copyright © 2014 John Wiley & Sons, Ltd.
Related JoVE Video
Decanoic acid grafted oligochitosan nanoparticles as a carrier for insulin transport in the gastrointestinal tract.
Carbohydr Polym
PUBLISHED: 02-20-2014
Show Abstract
Hide Abstract
The objective was to explore the potential of decanoic acid grafted oligochitosan nanoparticles (CSO-DA NPs) as a carrier for insulin. The insulin-loaded CSO-DA NPs obtained by varying the pH and concentrations of CSO and DA had a particle size of 200.6 ± 71.2 nm, with an entrapment efficiency and loading efficiency of 61.18% and 5.56%, respectively. An in vitro study of the formulation showed typical burst of insulin and pH-dependent characteristics. The NPs administered by the in situ loop method were effective in lowering the serum glucose level of rats which was based on the synergistic effect of adhesion of CSO and permeation enhancing effect of DA. In particular, the 50 IU/kg-dose of CSO-DA NPs reduced the serum glucose level by 57.18%. Histopathology investigations showed that the CSO-DA NPs had a low toxicity. Therefore, CSO-DA nanoparticles appear to be promising vehicles for insulin transport through the intestinal mucosa.
Related JoVE Video
Characterization of in vitro metabolites of TM-2, a potential antitumor drug, in rat, dog and human liver microsomes using liquid chromatography/tandem mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 02-18-2014
Show Abstract
Hide Abstract
TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-?-diacetoxy-2-?-benzoyloxy-5-?,20-epoxy-1,13-?-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semi-synthetic taxane derivative. Our previous study demonstrated that it is a promising taxane derivative. The in vitro comparative metabolic profile of a drug between animals and humans is a key issue that should be investigated at early stages of drug development to better select drug candidates. In this study, the in vitro metabolic pathways of TM-2 in rat, dog and human liver microsomes were established and compared.
Related JoVE Video
Effect of continuous positive airway pressure on serum cystatin C among obstructive sleep apnea syndrome patients.
Int Urol Nephrol
PUBLISHED: 02-15-2014
Show Abstract
Hide Abstract
The purpose of the present study was to evaluate the influence of continuous positive airway pressure (CPAP) on serum cystatin C, a novel biomarker of early renal impairment, among obstructive sleep apnea (OSA) patients.
Related JoVE Video
Hydroxyethyl starch conjugates for improving the stability, pharmacokinetic behavior and antitumor activity of 10-hydroxy camptothecin.
Int J Pharm
PUBLISHED: 02-04-2014
Show Abstract
Hide Abstract
10-Hydroxy camptothecin (10-HCPT)-hydroxyethyl starch (HES) conjugates were prepared to improve the water solubility, prolong the half-life in plasma and increase the antitumor efficacy of 10-HCPT, and the structures of the conjugates were confirmed by NMR and infrared spectroscopy. The 10-HCPT conjugates showed good sustained release effect in phosphate-buffered saline (PBS), rat plasma and liver homogenate. Meanwhile, 10-HCPT-HES conjugates achieved much lower IC50 and higher cytotoxicity effects than the free 10-HCPT on Hep-3B and SMMC-7721 cell lines. The pharmacokinetics results of 10-HCPT-HES conjugates demonstrated that the biological half-life of 10-HCPT was increased from 10 min to 2.94 h and 3.76 h, respectively, in comparison with the commercial 10-HCPT injection. The pharmacodynamics results indicated that 10-HCPT-HES conjugate had a better antitumor efficiency against nude mouse with Hep-3B tumor than the commercial 10-HCPT injection, and the inhibition ratio of tumor was 78.3% and 31.5%, respectively, at the dose of 1.0 mg/kg. These findings suggest that 10-HCPT-HES conjugate is a promising drug delivery system providing improved long circulating effect, greater stability and better antitumor effect.
Related JoVE Video
Nitrofurantoin enteric pellets with high bioavailability based on aciform crystalline formation by wet milling.
Pharm Dev Technol
PUBLISHED: 01-29-2014
Show Abstract
Hide Abstract
Abstract The aim of the present study was to grind nitrofurantoin (NF) with HPMC solution and to determine the dissolution and bioavailability of the enteric pellets prepared with the NF cogrounds and other excipients. During milling, crystalline transformation occurred - the aciform microcrystalline monohydrate II replaced the coarse crystal anhydrate ? and the particle size markedly reduced. In vitro test demonstrated that the enteric pellets prepared with NF cogrounds (4?h) revealed a faster dissolution than the commercial tablet and 50% was released within 30?min in the basic medium. Finally, an in vivo test was conducted in beagle dogs. The Cmax and AUC(0?24) of the pellets were 2.19?±?0.74??g/ml and 6.73?±?4.71??g/ml?h, respectively, while the corresponding values were 0.49?±?0.42??g/ml and 1.38?±?1.17??g/ml?h for the tablet. Thus, the bioavailability of the pellets was increased significantly. In conclusion, the wet grinding that reduced the particle size and created the microcrystalline played a major role in the acceleration of the dissolution of NF and, consequently, enhanced the bioavailability, and the wet grinding process offers an alternative approach to improve the dissolution and bioavailability of drugs with poor aqueous solubility.
Related JoVE Video
PEG-PLGA copolymers: their structure and structure-influenced drug delivery applications.
J Control Release
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
In the paper, we begin by describing polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA) which was chosen as a typical model copolymer for the construction of nano-sized drug delivery systems and also the types of PEG-PLGA copolymers that were eluted. Following this we examine the structure-influenced drug delivery applications including nanoparticles, micelles and hydrogels. After that, the preparation methods for nano-sized delivery systems are presented. In addition, the drug loading mode of PEG-PLGA micelles is divided into three aspects. Finally, the drug release profiles of PEG-PLGA micelles, both in terms of their in vitro and in vivo characteristics, are represented. PEG-PLGA copolymers are very suitable for the construction of micelles as carriers for insoluble drugs. This article reviews the structure and the different structure-influenced applications of PEG-PLGA copolymers, concentrating on the application of PEG-PLGA micelles.
Related JoVE Video
Circulatory bubble dynamics: from physical to biological aspects.
Adv Colloid Interface Sci
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
Bubbles can form in the body during or after decompression from pressure exposures such as those undergone by scuba divers, astronauts, caisson and tunnel workers. Bubble growth and detachment physics then becomes significant in predicting and controlling the probability of these bubbles causing mechanical problems by blocking vessels, displacing tissues, or inducing an inflammatory cascade if they persist for too long in the body before being dissolved. By contrast to decompression induced bubbles whose site of initial formation and exact composition are debated, there are other instances of bubbles in the bloodstream which are well-defined. Gas emboli unwillingly introduced during surgical procedures and ultrasound microbubbles injected for use as contrast or drug delivery agents are therefore also discussed. After presenting the different ways that bubbles can end up in the human bloodstream, the general mathematical formalism related to the physics of bubble growth and detachment from decompression is reviewed. Bubble behavior in the bloodstream is then discussed, including bubble dissolution in blood, bubble rheology and biological interactions for the different cases of bubble and blood composition considered.
Related JoVE Video
Magnetic resonance characteristics of adult-onset Lhermitte-Duclos disease: An indicator for active cancer surveillance?
Mol Clin Oncol
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Lhermitte-Duclos disease (LDD) is a rare, non-cancerous entity characterized by enlarged, abnormally developed cerebellar folia containing dysplastic cells. Symptomatic LDD is commonly observed in adults (adult-onset LDD, aLDD) as an isolated condition or associated with Cowden's disease (CD). The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and the underlying pathological findings in 7 cases of aLDD, with emphasis on the association with CD and the need for active cancer surveillance once the diagnosis of LDD is confirmed. The MRI findings along with the clinical and histopathological data collected from 7 patients with aLDD were retrospectively reviewed. The diagnosis of CD was based on a range of clinical characteristics, according to the International Cowden Consortium Criteria. A thorough review of the published data was conducted and our results indicated that all 7 cases shared similar MRI characteristics, whether the aLDD was sporadic (2 cases) or associated with CD (5 cases), including a highly typical non-enhancing striated MRI appearance of thickened folia, consisting of alternating bands on T1- and T2-weighted images. On gross examination, the involved cerebellar folia were distorted and enlarged, whereas the histopathological examination revealed that the molecular layer was widened and occupied by abnormal ganglion cells. Moreover, a reduction in the number or absence of the Purkinje cells and hypertrophy of the granular cell layer were observed. Our findings were consistent with the diagnosis of LDD. Variable levels of vacuolization of the white matter and the molecular layer were observed in all the cases. Notably, CD34 immunohistochemical analysis revealed the presence of angiogenesis within the lesions. aLDD associated with CD exhibited no pathological or immunohistochemical characteristics that were distinct from those of isolated aLDD. Of the 7 cases of aLDD, 5 presented with symptoms suggestive of CD, which is a syndrome associated with a high risk of multiple benign and malignant neoplasms. In conclusion, aLDD exhibits characteristic MRI and histopathological findings and displays a strong association with CD. Therefore, we recommend that the MRI diagnosis of aLDD triggers active cancer surveillance and preventive care.
Related JoVE Video
Determination of larotaxel and its metabolites in rat plasma by liquid chromatography-tandem mass spectrometry: application for a pharmacokinetic study.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
A sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for determination of larotaxel (LTX) and its active metabolites (M1, M2 and M3) in rat plasma. The analytes were extracted by one-step protein precipitation and separated on a Capcell pak C18 column (2.0 mm × 100 mm; 2 ?m; Shiseido) using methanol-water as mobile phase at a flow rate of 0.2 mL min(-1) in gradient mode. The method was validated over the concentration range of 2.5-1250 ng mL(-1) for LTX and 1.0-500 ng mL(-1) for M1, respectively, while M2 and M3 were monitored semi-quantitatively and quantified as M1 equivalents. Intra- and inter-day accuracy and precision were within the acceptable limits of less than 15% at all concentrations. Coefficients of correlation (r) for the calibration curves were more than 0.99 for all analytes. The quantitation method was successfully applied for simultaneous estimation of LTX and its metabolites in a pharmacokinetic study after oral administration at different doses of 10, 20, and 40 mg/kg and intravenous administration at the dose 10 mg/kg to Wistar rats, respectively. The results indicated that larotaxel has linear pharmacokinetic characteristics in rats after oral administration and its absolute bioavailability in rats was 12.24%.
Related JoVE Video
Metabolism of TM-2, a potential antitumor drug, in rats by using LC-MS.
J Sep Sci
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
TM-2 (13-(N-Boc-3-i-butylisoserinoyl-4,10-?-diacetoxy-2-?-benzoyloxy-5-?-20-epoxy-1,13-?-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene) is a novel semisynthetic taxane derivative. Our previous study suggested that TM-2 is a promising antitumor analogue. In this paper, the metabolism of TM-2 was investigated in rats following intravenous administration. Two different types of mass spectrometry-hybrid linear trap quadrupole orbitrap (LTQ-Orbitrap) mass spectrometry and triple-quadrupole tandem (QQQ) mass spectrometry-were employed to acquire structural information of TM-2 metabolites. A total of 17 components were identified as the metabolites of TM-2 in bile, feces, and urine samples. Accurate mass measurement using LC-LTQ-Orbitrap-MS was used to determine the accurate mass data and elemental composition of metabolites thereby confirming the proposed structures of the metabolites. The metabolites proposed were mainly oxidates of TM-2, including methoxy, hydroxyl, dihydroxy, and trihydroxyl analogues. The major metabolic pathway of TM-2 was the hydroxylation of the taxane ring or the lateral chain. These important metabolic data serve as a useful resource to support further research of TM-2.
Related JoVE Video
Molecular cloning, bioinformatics analysis and functional characterization of HWTX-XI toxin superfamily from the spider Ornithoctonus huwena.
Peptides
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
Spider venom contains a very valuable repertoire of natural resources to discover novel components for molecular diversity analyses and therapeutic applications. In this study, HWTX-XI toxins from the spider venom glands of Ornithoctonus huwena which are Kunitz-type toxins (KTTs) and were directly cloned, analyzed and functionally characterized. To date, the HWTX-XI superfamily consists of 38 members deduced from 121 high-quality expressed sequence tags, which is the largest spider KTT superfamily with significant molecular diversity mainly resulted from cDNA tandem repeats as well as focal hypermutation. Among them, HW11c40 and HW11c50 may be intermediate variants between native Kunitz toxins and sub-Kunitz toxins based on evolutionary analyses. In order to elucidate their biological activities, recombinant HW11c4, HW11c24, HW11c27 and HW11c39 were successfully expressed, further purified and functionally characterized. Both HW11c4 and HW11c27 display inhibitory activities against trypsin, chymotrypsin and kallikrein. Moreover, HW11c4 is also an inhibitor relatively specific for Kv1.1 channels. HW11c24 and HW11c39 are found to be inactive on chymotrysin, trypsin, kallikrein, thrombin and ion channels. These findings provide molecular evidence for toxin diversification of the HWTX-XI superfamily and useful molecular templates of serine protease inhibitors and ion channel blockers for the development of potentially clinical applications.
Related JoVE Video
PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
In this content, a small molecular ligand of prostate specific membrane antigen (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG) copolymers with different block lengths were synthesized to construct a satisfactory drug delivery system. Four different docetaxel-loaded polymeric micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm as characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Optimization of the prepared micelles was conducted based on short-term stability and drug-loading content. The results showed that optimized systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs with the same ratio of hydrophilic/hydrophobic chain length displayed similar sustained release behaviors. The cytotoxicity of the optimized targeted DTX-PCL12K-PEG5K-SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL12K-mPEG5K micelles (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that the targeted micelles had a much lower IC50 than their non-targeted counterparts (48 h: 0.87±0.27 vs 13.48±1.03 µg/ml; 72 h: 0.02±0.008 vs 1.35±0.54 µg/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence intensity than that of PMs1 after 4 h incubation. According to these results, the novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great promise for the treatment of prostatic cancer.
Related JoVE Video
Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix.
Drug Dev Ind Pharm
PUBLISHED: 12-11-2013
Show Abstract
Hide Abstract
Abstract The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5??m, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210?min, exhibited sustained release pattern within 8?h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.
Related JoVE Video
Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.
Drug Deliv
PUBLISHED: 11-05-2013
Show Abstract
Hide Abstract
Abstract The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-?-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170?nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100?nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14?d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22??m millipore membrane filter.
Related JoVE Video
[Geographic distribution and gene sequencing of Paragonimus westermani in some areas of Guangdong Province].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
To investigate the current distribution of Paragonimus westermani in Guangdong Province.
Related JoVE Video
Lipid emulsions in parenteral nutrition: current applications and future developments.
Expert Opin Drug Deliv
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
A parenteral lipid emulsion (LE), used as a key source of energy, essential fatty acids (FAs), and fat-soluble vitamins, is an integral part of a parenteral nutrition (PN) regimen. The conventional LEs, such as soybean oil (SO)-based emulsions, have caused concerns about the potential adverse effects involving oxidative stress, inflammation, and immune response probably because of undesirable FA composition.
Related JoVE Video
[Determination of unknown impurities in cefotiam hexetil by HPLC-MS/MS].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
To detect unknown impurities in raw drug material of cefotiam hexetil.
Related JoVE Video
Bioinformatics analysis of a non-specific nuclease from Yersinia enterocolitica subsp. palearctica.
Comput Biol Chem
PUBLISHED: 07-30-2013
Show Abstract
Hide Abstract
In this paper, the physical and chemical characteristics, biological structure and function of a non-specific nuclease from Yersinia enterocolitica subsp. palearctica (Y. NSN) found in our group were studied using multiple bioinformatics approaches. The results showed that Y. NSN had 283 amino acids, a weight of 30,692.5ku and a certain hydrophilic property. Y. NSN had a signal peptide, no transmembrane domains and disulphide bonds. Cleavage site in Y. NSN was between pos. 23 and 24. The prediction result of the secondary structure showed Y. NSN was a coil structure-based protein. The ratio of ?-helix, ?-folded and random coil were 18.73%, 16.96% and 64.31%, respectively. Active sites were pos. 124, 125, 127, 157, 165 and 169. Mg(2+) binding site was pos. 157. Substrate binding sites were pos. 124, 125 and 169. The analysis of multisequencing alignment and phylogenetic tree indicated that Y. NSN shared high similarity with the nuclease from Y. enterocolitica subsp. enterocolitica 8081. The enzyme activity results showed that Y. NSN was a nuclease with good thermostability.
Related JoVE Video
Parenteral formulation of larotaxel lipid microsphere tackling poor solubility and chemical instability.
Int J Pharm
PUBLISHED: 07-26-2013
Show Abstract
Hide Abstract
The purpose of this study was to develop a parenteral larotaxel lipid microsphere (LTX-LM) and evaluate its stability. The preformulation study showed that LTX possessed poor solubility (0.057?g/mL in aqueous phase) and chemical instability. LM was selected as the drug carrier due to its higher drug-loading capacities, higher physicochemical stability and reduced irritation and toxicity. High speed shear mixing and high-pressure homogenization were employed to prepare the LTX-LM. Particle size distribution (PSD), zeta-potential, drug content and entrapment efficiency (EE) were taken as indexes to optimize formulations. The dissolution studies were performed using a ZRS-8G dissolution apparatus according to the paddle method. Degradation kinetics test, freezing and thawing test and long term stability test were combined to evaluate the physicochemical stability of LTX-LM. From the degradation kinetics results, the shelf lives (T90%) of LTX in LM at 25 and 4°C (165, 555 days) were about 20 times as long as those in aqueous phase (200, 676h), which were dramatically prolonged. The activation energies in aqueous solution and in LM calculated from the slopes were 41.93 and 42.25kJ/mol. And its frequency factors (A) were 4.9×10(3)/s and 2.3×10(2)/s, respectively. Freezing and thawing test showed the PSD of LTX-LM became larger and wider increasing from 166.9±53.2nm to 257.4±85.5nm with more freeze-thaw cycles. From the long term stability test results, all the parameters changes were in qualified range.
Related JoVE Video
[Role of autophagy on cobrotoxin induced cell death of A549].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
It has been proven that cobrotoxin has anti-tumor effect while its role in lung cancer is rarely studied. The aim of this study is to assay the anti-tumor effect of cobrotoxin in cell line A549, and also to explore its possible mechanism related to autophagy and P38-MARK pathway.
Related JoVE Video
Viscosity measurement based on shear-wave laser speckle contrast analysis.
J Biomed Opt
PUBLISHED: 07-20-2013
Show Abstract
Hide Abstract
ABSTRACT. Tissue viscosity is correlated with tissue pathological changes and provides information for tissue characterization. In this study, we report an optical method to track continuous shear-wave propagation at centimeter depths in an optically turbid medium. Shear-wave attenuation coefficients were measured at multiple frequencies using shear-wave laser speckle contrast analysis (SW-LASCA) to quantitatively estimate tissue viscosity using the Voigt model. Shear waves were generated within tissue-mimicking phantoms by an amplitude-modulated ultrasound (modulation frequency: 100 to 600 Hz) and tracked by time-resolved laser speckle contrast difference received on a charged-coupled device camera. Averaged contrast difference over a selected time window was related to shear-wave amplitude and used to calculate the shear-wave attenuation coefficient. Phantoms of varying viscosities (0.1 and 0.3 Pa s) were studied. Attenuation coefficients for different shear-wave frequencies (100 to 600 Hz) were calculated. Derived viscosity values had a maximum standard deviation of 9%, and these values were consistent with the independent measurements reported in a previous study using nonoptical methods.
Related JoVE Video
Improving cabazitaxel chemical stability in parenteral lipid emulsions using cholesterol.
Eur J Pharm Sci
PUBLISHED: 07-09-2013
Show Abstract
Hide Abstract
Intravenous lipid emulsions of cabazitaxel (CLEs) with a high stability were prepared by adding cholesterol (CH) to provide a new and more suitable delivery system for its administration. The factors affecting CLEs, such as the solubility of cabazitaxel in various oils, different kinds of lecithin, pH, different types of oil phases, and different concentrations of lipoid E80®, CH and poloxamer 188 were investigated systematically. The degradation of cabazitaxel in aqueous solution and lipid emulsion both followed pseudo first-order kinetics. A degradation mechanism was suggested by the U-shaped pH-rate profile of cabazitaxel. A formulation containing 0.5% (w/v) CH and another formulation without CH were made to investigate the protective influence of CH on the chemical stability of CLEs. The activation energy of the two formulations was calculated to be 65.74±6.88 and 54.24±1.43kJ/mol (n=3), respectively. Compared with the untreated CH, the shelf-life of cabazitaxel with added CH was longer, namely 134.0±23.4days versus 831.4±204.4days (n=3) at 4°C. This indicates that the addition of CH significantly improved the lifetime of cabazitaxel in intravenous lipid emulsions. The hydrogen bonding that takes place between cabazitaxel and CH accounts for the protective effect of CH on the chemical stability of CLEs in two ways: preventing cabazitaxel from leaking and hydrolyzing in aqueous solution and hindering hydrolysis in the oil phase. Finally, the hypothesis was confirmed by LC/TOFMS and Fourier-transform infrared-spectroscopy. As a result, CLEs were obtained successfully by the addition of CH and were stable enough to allow further research.
Related JoVE Video
Catalytic conversion of carbohydrates into 5-hydroxymethylfurfural over cellulose-derived carbonaceous catalyst in ionic liquid.
Bioresour. Technol.
PUBLISHED: 06-23-2013
Show Abstract
Hide Abstract
Three environmental-benign and low-cost carbon-based solid acid catalysts containing -SO3H, -COOH and phenolic -OH groups were prepared and used for the conversion of glucose into 5-hydroxymethylfurfural (HMF) in ionic liquid 1-butyl-3-methylimidazolium chloride ([BMIM]Cl). The results demonstrated that cellulose-derived carbonaceous catalyst (CCC) possessed the highest catalytic activity, which resulted in 46.4% HMF yield at 160°C for only 15 min. In addition, the reaction kinetics for the conversion of glucose into HMF over CCC was fitted with the first-order rate equation. The slightly-deactivated CCC after four successive reaction runs could be easily regenerated by a simple carbonization and sulfonation process. More gratifyingly, the combination of CCC and [BMIM]Cl were confirmed to be suitable for converting other carbohydrates such as fructose, sucrose, maltose, cellobiose, starch and cellulose into HMF. Particularly, a plausible mechanism involving hydrolysis, isomerization and dehydration for the conversion of carbohydrates into HMF was also proposed.
Related JoVE Video
Improved oral bioavailability of core-shell structured beads by redispersion of the shell-forming nanoparticles: Preparation, characterization and in vivo studies.
Colloids Surf B Biointerfaces
PUBLISHED: 06-08-2013
Show Abstract
Hide Abstract
In order to increase the dissolution rate and oral bioavailability of bifendate, coated beads with core-shell structure were prepared via a combination use of wet media milling method and bead layering process. Hydroxypropyl cellulose (HPC-SL) and sodium lauryl sulfate (SLS) were found to be the best pair to stabilize the nanosuspension during milling process. A 10:1 ratio of mixture of mannitol and SLS was chosen as most suitable coating matrix to maintain the redispersability of dried nanoparticles in the shell of beads. The mean particle size of the nanosuspension was 139nm and the zeta potential was -20.2mV. Nanoscale bifendate particles with a mean diameter of 360nm could be generated when redispersing the prepared beads in water. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that the crystalline state of the drug was not changed. The stability test confirmed that coated beads showed no distinct difference in particle size and dissolution velocity during 6 month storage while liquid nanosuspension was stable no more than 3 weeks. Dissolution rate of coated beads was increased significantly compared with commercially available pills. Likewise, the Cmax and AUC (0?24) of nanosuspension based beads in beagle dogs were 2.40-fold and 1.66-fold greater than that of commercially available pills, respectively. The present work is a reliable approach to stabilize nanosuspension based product, and improve dissolution velocity and bioavailability of poor soluble drugs.
Related JoVE Video
A novel UPLC-ESI-MS/MS method for the quantitation of disulfiram, its role in stabilized plasma and its application.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 06-05-2013
Show Abstract
Hide Abstract
Disulfiram (DSF) has been used to treat alcoholism for many years and it has been suggested to play a key role in combatting many kinds of tumors. However, disulfiram has complex pharmacokinetics and is rapidly eliminated which limits its use as a tumor treatment. Therefore, a rapid and sensitive analytical method based on ultra performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for the determination of disulfiram in rat plasma. Blood samples were pre-stabilized with a stabilizing agent and then plasma was obtained and subjected to solid phase extraction (SPE), and chromatographed on a Phenomenex Kinetex(®) XB C18 column with gradient elution using a mobile phase consisting of acetonitrile-water (containing 0.1% formic acid and 1mM ammonium acetate) at a flow rate of 0.2mL/min for 3min. Multiple reactions monitoring in positive mode was carried out with disulfiram at 296.95/115.94 and diphenhydramine (internal standard, IS) at 256.14/167.02 over a linear range from 0.6 to 1200ng/mL. The extraction recovery of disulfiram for different concentrations ranged from 75.7% to 78.3%. The intra- and inter-day precision was less than 8.93% and 12.39%, respectively, and the accuracy was within ±7.75%. The validated method was successfully applied to a pharmacokinetic study of disulfiram in rat plasma after oral administration of a dose of 180mg/kg.
Related JoVE Video
Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-20-2013
Show Abstract
Hide Abstract
Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a "molecular rotor" embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component.
Related JoVE Video
Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy.
Chin. Med. J.
PUBLISHED: 05-16-2013
Show Abstract
Hide Abstract
Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE).
Related JoVE Video
Transcriptome analysis of venom glands from a single fishing spider Dolomedes mizhoanus.
Toxicon
PUBLISHED: 05-04-2013
Show Abstract
Hide Abstract
The spider venom is a large pharmacological repertoire composed of different types of bioactive peptide toxins. Despite the importance of spider toxins in capturing terrestrial prey and defending themselves against predators, we know little about the venom components from the spider acting on the fish. Here we constructed a cDNA library of a pair of venomous glands from a single fish-hunting spider Dolomedes mizhoanus. A total of 356 high-quality expressed sequence tags (ESTs) were obtained from the venom gland cDNA library and analyzed. These transcripts were further classified into 45 clusters (19 contigs and 26 singletons), most of which encoded cystine knot toxins (CKTs) and non-CKTs. The ESTs coding for 53 novel CKT precursors were abundant transcripts in the venom glands of the spider D. mizhoanus, accounting for 76% of the total ESTs, the precursors of which were grouped into six families based on the sequence identity and the phylogenetic analysis. In addition, the non-CKTs deduced from 21% of the total ESTs were annotated by Gene Ontology terms and eukaryotic orthologous groups. Fifty-five CKT precursors deduced from 273 ESTs are the largest dataset for a single spider specimen to date. The results may contribute to discovering novel potential drug leads from spider venoms and a better understanding of the evolutionary relationship of the spider toxin.
Related JoVE Video
Effects of single and combined genotypes of MC4R and POU1F1 genes on two production traits in Langshan chicken.
Mol. Biol. Rep.
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
The objective of this study was to analyze the effects of single and combined genotypes of MC4R and POU1F1 genes in Chinese well-known indigenous chicken (Langshan chicken) population. Genetic variants within MC4R gene and POU1F1 gene were screened through PCR-SSCP and DNA sequencing methods. A C/T mutation at nt 944 in MC4R gene (NC_006089.2:g. 944C>T) and a G/A mutation at nt 3109 in POU1F1 gene (NC_006088.2:g. 3109 G>A) were identified. Associations between the mutations of the two genes with two production traits were analyzed. The results showed that, at MC4R locus, individuals with BB and AB genotypes had highly significantly higher body weight at 16 weeks (p < 0.01) than did those with the AA genotype. And, individuals within AA and AB genotypes had significantly higher egg numbers at 300 days (p < 0.05). At POU1F1 locus, individuals with CD genotype had higher body weight at 16 weeks and egg numbers at 300 days (p < 0.05). Furthermore, combined genotypes from these two loci were found to be associated with egg numbers at 300 days (p < 0.05). The individuals within combined genotype AB/CD had higher egg production. Therefore, variations identified within the MC4R and POU1F1genes are suitable for future use in identifying chickens with the genetic potential of higher body weight and reproductive traits, at least in the population of Langshan chickens.
Related JoVE Video
In vitro/in vivo evaluation of felodipine micropowders prepared by the wet-milling process combined with different solidification methods.
Drug Dev Ind Pharm
PUBLISHED: 04-25-2013
Show Abstract
Hide Abstract
Abstract In order to improve the in vitro dissolution rate and in vivo oral bioavailability of the poorly water soluble drug, felodipine (FELO), the wet-milling process was employed involving co-grinding with HPMC E5 and the in vitro release rate as investigated. After solidification by spray drying or freeze drying, the microsized powders were characterized in terms of their size, morphology, and in vitro dissolution rate. The oral bioavailability of this dry powder for suspension was evaluated in rats. After milling with 8% HPMC E5 and freeze drying, the powder mixture had an average particle size of 2.249?±?1.497??m and displayed an excellent dissolution rate of up to 93.2% within 10?minutes. DSC and PXRD investigations confirmed the absence of any crystal transformation during the wet-milling process. Using two different solidification methods, powders were stable for 6 months with regard to their in vitro dissolution rate. Significantly improved bioavailability was obtained for the wet-milled suspension before solidification and freeze dried powders with 6.8- (p??0.05) in bioavailability was seen for the spray dried powders. These effects suggest that the solidification method plays an important role in modifying the bioavailability of FELO after wet milling. Consequently, wet-milling is an effective technique to enhance the bioavailability of FELO and to maintain these benefits, freeze-drying is a feasible approach to solidifying the wet-milled suspension for industrial applications.
Related JoVE Video
DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors.
Int. J. Cancer
PUBLISHED: 04-04-2013
Show Abstract
Hide Abstract
Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer.
Related JoVE Video
Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats.
J Pharm Biomed Anal
PUBLISHED: 03-17-2013
Show Abstract
Hide Abstract
With the purpose to carry out the pharmacokinetic studies of 10-hydroxy camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated. The analytes, 10-HCPT and the internal standard, Diphenhydramine hydrochloride were extracted with ethyl acetate-isopropanol (95:5, v/v) and separated on an ACQUITY UPLC™ BEH C18 column using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) with a linear gradient program. With positive ion electrospray ionization (ESI), the analytes were monitored on a triple quadrupole mass spectrometer in the multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over the concentration ranges of 0.5-2500ng/mL. The intra- and inter-day precisions were less than 9.8% and 10.8%, respectively. The accuracy was within 12.1%. The mean recoveries of 10-HCPT at three concentrations of 2.5, 100, 2000ng/mL were higher than 87.2%. Commercial 10-HCPT injection and 10-HCPT-HES conjugate were administered intravenously at an equal dose of 10-HCPT at 0.5mg/kg. The biological half-life of conjugate was increased significantly from 10min to 3.15h and the bioavailability was 40 times higher than 10-HCPT injection. Consequently, the proposed UPLC-ESI-MS/MS method was proved to be sensitive, specific and reliable to analyze 10-HCPT in biological samples; 10-HCPT and HES conjugate is a promising strategy for delivery of 10-HCPT with prolonged half time and improved bioavailability.
Related JoVE Video
Single bubble acoustic characterization and stability measurement of adherent microbubbles.
Ultrasound Med Biol
PUBLISHED: 03-06-2013
Show Abstract
Hide Abstract
This article examines how the acoustic and stability characteristics of single lipid-shelled microbubbles (MBs) change as a result of adherence to a target surface. For individual adherent and non-adherent MBs, the backscattered echo from a narrowband 2-MHz, 90-kPa peak negative pressure interrogation pulse was obtained. These measurements were made in conjunction with an increasing amplitude broadband disruption pulse. It was found that, for the given driving frequency, adherence had little effect on the fundamental response of an MB. Examination of the second harmonic response indicated an increase of the resonance frequency for an adherent MB: resonance radius increasing of 0.3 ± 0.1 ?m for an adherent MB. MB stability was seen to be closely related to MB resonance and gave further evidence of a change in the resonance frequency due to adherence.
Related JoVE Video
Date fruit: chemical composition, nutritional and medicinal values, products.
J. Sci. Food Agric.
PUBLISHED: 03-05-2013
Show Abstract
Hide Abstract
Date fruit has served as a staple food in the Arab world for centuries. Worldwide production of date fruit has increased almost threefold over the last 40 years, reaching 7.68 million tons in 2010. Date fruit can provide many essential nutrients and potential health benefits to the consumer. Date fruit goes through four ripening stages named kimri, khalal, rutab and tamer. The main chemical components of date fruit include carbohydrates, dietary fibre, enzymes, protein, fat, minerals, vitamins, phenolic acids and carotenoids. The chemical composition of date fruit varies according to ripening stage, cultivar, growing environment, postharvest conditions, etc. The nutritional and medicinal activities of date fruit are related to its chemical composition. Many studies have shown that date fruit has antioxidant, antimutagenic, anti-inflammatory, gastroprotective, hepatoprotective, nephroprotective, anticancer and immunostimulant activities. Various date fruit-based products such as date syrup, date paste, date juice and their derived products are available. Date by-products can be used as raw materials for the production of value-added products such as organic acids, exopolysaccharides, antibiotics, date-flavoured probiotic-fermented dairy produce, bakery yeasts, etc. In this paper the chemical composition and nutritional and medicinal values of date fruit as well as date fruit-based products are reviewed.
Related JoVE Video
The evaluation of patient-specific factors associated with meniscal and chondral injuries accompanying ACL rupture in young adult patients.
Knee Surg Sports Traumatol Arthrosc
PUBLISHED: 02-26-2013
Show Abstract
Hide Abstract
To evaluate patient-specific factors, including the mechanism of injury, time from the injury, activity level after the initial trauma, re-injury and body mass index (BMI), as risk factors for meniscal and chondral injuries accompanying anterior cruciate ligament (ACL) rupture.
Related JoVE Video
Increased dissolution and oral absorption of itraconazole/Soluplus extrudate compared with itraconazole nanosuspension.
Eur J Pharm Biopharm
PUBLISHED: 02-26-2013
Show Abstract
Hide Abstract
The purpose of this article was to compare the in vitro and in vivo profiles of itraconazole (ITZ) extrudates and nanosuspension separately prepared by two different methods. And it was proved truly to form nanocrystalline and amorphous ITZ characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrum (FTIR), transmission electron microscope (TEM), and scanning electron microscope (SEM). The release of ITZ/Soluplus solid dispersions with amorphous ITZ was almost complete while only 40% release was obtained with ITZ nanocrystals. The amorphous state need not to cross over the crystal lattice energy upon dissolution while the crystalline need to overcome it. In the in vivo assay, the AUC(0-t) and Cmax of ITZ/Soluplus were 6.9- and 11.6-time higher than those of pure ITZ. The formulation of the extrudate had an AUC(0-t) and Cmax similar to those of ITZ and also OH-ITZ compared with the commercial capsule (Sporanox®). The relative bioavailability values with their 95% confidence limit were calculated to be 98.3% (92.5-104.1%) and 101.3% (97.9-104.1%), respectively. The results of this study showed increased dissolution and bioavailability of the solid dispersion of Soluplus-based carrier loading ITZ prepared by HME compared with the ITZ nanosuspension prepared by wet milling.
Related JoVE Video
A critical review of physiological bubble formation in hyperbaric decompression.
Adv Colloid Interface Sci
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
Bubbles are known to form in the body after scuba dives, even those done well within the decompression model limits. These can sometimes trigger decompression sickness and the dive protocols should therefore aim to limit bubble formation and growth from hyperbaric decompression. Understanding these processes physiologically has been a challenge for decades and there are a number of questions still unanswered. The physics and historical background of this field of study is presented and the latest studies and current developments reviewed. Heterogeneous nucleation is shown to remain the prime candidate for bubble formation in this context. The two main theories to account for micronuclei stability are then to consider hydrophobicity of surfaces or tissue elasticity, both of which could also explain some physiological observations. Finally the modeling relevance of the bubble formation process is discussed, together with that of bubble growth as well as multiple bubble behavior.
Related JoVE Video
Induction of pluripotency in mouse somatic cells with lineage specifiers.
Cell
PUBLISHED: 02-13-2013
Show Abstract
Hide Abstract
The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model" in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.
Related JoVE Video
A novel non-hydrolytic protein from Pseudomonas oryzihabitans enhances the enzymatic hydrolysis of cellulose.
J. Biotechnol.
PUBLISHED: 02-08-2013
Show Abstract
Hide Abstract
Several kinds of protein such as the expansin, expansin-like proteins and LPMOs (lytic polysaccharide monooxygenases) are known to exert enhancement effects on cellulase activity. In this study, a novel cellulase synergistic protein named POEP1 was purified from the culture filtrate of Pseudomonas oryzihabitans CGMCC 6169, and was homogeneous on SDS-PAGE with a molecular weight of 60kDa. Mass spectrometry analysis indicated that it was an unknown protein without sequence similarity to the expansin and expansin-like proteins. Evaluation of the enzymatic hydrolysis of filter paper revealed that POEP1 had no cellulase activity but displayed high synergistic activity of 364% at a cellulase concentration of 0.1FPU/g of filter paper. When a mixture containing 0.6FPU cellulase and 700?g POEP1 per g of cellulose was evaluated, the maximal sugar yield was achieved, which was 2.2-fold greater than that with the cellulase alone. POEP1 was found to have functional similarity to the expansin and expansin-like proteins, which could decrease both the hydrogen-bond intensity and crystallinity, and cause the filter paper disruption. This study provided evidence for the existence of novel bacterial proteins in nature serving the same function as expansin and expansin-like proteins.
Related JoVE Video
A stable and practical etoposide-containing intravenous long-/medium-chain triglycerides-based lipid emulsion formulation: pharmacokinetics, biodistribution, toxicity, and antitumor efficacy.
Expert Opin Drug Deliv
PUBLISHED: 02-04-2013
Show Abstract
Hide Abstract
This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS).
Related JoVE Video
Ultrasound imaging velocimetry: effect of beam sweeping on velocity estimation.
Ultrasound Med Biol
PUBLISHED: 02-03-2013
Show Abstract
Hide Abstract
As an emerging flow-mapping tool that can penetrate deep into optically opaque media such as human tissue, ultrasound imaging velocimetry has promise in various clinical applications. Previous studies have shown that errors occur in velocity estimation, but the causes have not been well characterised. In this study, the error in velocity estimation resulting from ultrasound beam sweeping in image acquisition is quantitatively investigated. The effects on velocity estimation of the speed and direction of beam sweeping relative to those of the flow are studied through simulation and experiment. The results indicate that a relative error in velocity estimation of up to 20% can be expected. Correction methods to reduce the errors under steady flow conditions are proposed and evaluated. Errors in flow estimation under unsteady flow are discussed.
Related JoVE Video
Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution.
Cancer Chemother. Pharmacol.
PUBLISHED: 01-28-2013
Show Abstract
Hide Abstract
Larotaxel is a new taxane compound with poor solubility. The aim of this study is to develop a new formulation to locate the poorly soluble drug and compare the pharmacokinetics and tissue distribution of larotaxel-loaded microsphere (LTX-LM) with the solution form larotaxel-solution (LTX-solution).
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.