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Find video protocols related to scientific articles indexed in Pubmed.
Nanomedicines Based Drug Delivery Systems For Anti-Cancer Targeting And Treatment.
Curr Drug Deliv
PUBLISHED: 08-22-2014
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Cancer is defined as an uncontrolled growth of abnormal cells. Current treatment strategies for cancer include a combination of radiation, chemotherapy and surgery. The long-term use of conventional drug delivery systems for cancer chemotherapy leads fatal damage of normal proliferate cells and this is particularly used for the management of solid tumors, where utmost tumor cells do not invade quickly. A targeted drug delivery system (TDDS) is a system, which releases the drug at a preselected biosite in a controlled manner. Nanotechnology based delivery systems are making a significant impact on cancer treatment and polymers play key role in the development of nanopraticlulate carriers for cancer therapy. Some important technological advantages of nanotherapeutic drug delivery systems (NDDS) includes prolonged half-life, improved biodistribution, increased the circulation time of the drug, controlled and sustained release of the drug, versatility of root of administration, increased intercellular concentration of drug and many more. This review covers the current research on polymer based anticancer agents, the rationale for development of these polymer therapeutics systems and discusses the benefits and challenges of cancer nanomedicines including polymer-drug conjugates, micelles, dendrimers, immunoconjugates, liposomes, nanoparticles.
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Cationic Nanoemulsions Bearing Ciprofloxacin Surf-Plexes Enhances Its Therapeutic Efficacy in Conditions of E. coli Induced Peritonitis and Sepsis.
Pharm. Res.
PUBLISHED: 03-15-2014
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Chitosan (CH) coated ciprofloxacin-sodium deoxycholate surfplex (CFn-SDC) loaded nanoemulsion (LE-CH-CFn-SDC) developed in order to improve tissue penetration of the CFn as well as to mop up the endotoxin (Lipopolysaccharides or LPS) released from bacteria during antibiotic treatment.
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Molecular dissection of phage endolysin: an interdomain interaction confers host specificity in Lysin A of Mycobacterium phage D29.
J. Biol. Chem.
PUBLISHED: 03-13-2014
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Mycobacterium tuberculosis has always been recognized as one of the most successful pathogens. Bacteriophages that attack and kill mycobacteria offer an alternate mechanism for the curtailment of this bacterium. Upon infection, mycobacteriophages produce lysins that catalyze cell wall peptidoglycan hydrolysis and mycolic acid layer breakdown of the host resulting in bacterial cell rupture and virus release. The ability to lyse bacterial cells make lysins extremely significant. We report here a detailed molecular dissection of the function and regulation of mycobacteriophage D29 Lysin A. Several truncated versions of Lysin A were constructed, and their activities were analyzed by zymography and by expressing them in both Escherichia coli and Mycobacterium smegmatis. Our experiments establish that Lysin A harbors two catalytically active domains, both of which show E. coli cell lysis upon their expression exclusively in the periplasmic space. However, the expression of only one of these domains and the full-length Lysin A caused M. smegmatis cell lysis. Interestingly, full-length protein remained inactive in E. coli periplasm. Our data suggest that the inactivity is ensued by a C-terminal domain that interacts with the N-terminal domain. This interaction was affirmed by surface plasmon resonance. Our experiments also demonstrate that the C-terminal domain of Lysin A selectively binds to M. tuberculosis and M. smegmatis peptidoglycans. Our methodology of studying E. coli cell lysis by Lysin A and its truncations after expressing these proteins in the bacterial periplasm with the help of signal peptide paves the way for a large scale identification and analysis of such proteins obtained from other bacteriophages.
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Evidence of a conserved intrinsically disordered region in the C-terminus of the stringent response protein Rel from mycobacteria.
FEBS Lett.
PUBLISHED: 01-09-2014
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The RelA/SpoT enzyme produces (p)ppGpp that helps the bacterium survive during stress. The domains present in it are interspersed with connecting linkers whose functions have been poorly elucidated. We rationally analyzed the sequence and structural property of the regulatory C-terminal region in the Rel family of proteins and report the presence of an intrinsically disordered region between two successive domains in this region that are separated by a defined amino acid sequence length. We show that the length and secondary structure of this linker are conserved in Rel proteins, further signifying its importance in rendering flexibility for domain movement and domain-domain interaction.
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Craniovertebral junction melanocytoma: a case report.
Turk Neurosurg
PUBLISHED: 10-09-2013
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Melanocytomas are rare melanocytic tumors of the central nervous system and its presence at the foramen magnum is extremely rare. We report a case of a 55-year-old male presenting with progressive quadriparesis over one year. Imaging showed a well-defined intradural extramedullary lobulated mass at craniovertebral junction towards the left side and extending to left C2-3 neural foramina. Patient was operated through foramen magnum approach with near total excision of tumor. On a ten-month follow up, he was ambulatory with normal motor power on right side of body and left lower limb and with motor power of 4-/5 in left upper limb. Histopathology and immunohistochemistry confirmed the lesion to be a melanocytoma.
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Gemcitabine-loaded smart carbon nanotubes for effective targeting to cancer cells.
J Drug Target
PUBLISHED: 03-14-2013
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Carbon nanotubes (CNTs) are the three-dimensional sp(2) hybridized nano-containers that have attracted considerable interest in drug delivery by offering potential advantages such as biocompatibility, non-immunogenicity, high loading efficiency, intrinsic stability and low toxicities. The aim of the present investigation was to assess the potential of gemcitabine-loaded folic acid (FA) conjugated multi-walled CNTs (GEM/FA-NT) for targeting to breast cancer cells. Pristine MWCNTs was functionalized by FA followed by carboxylation, acylation and amidation and characterized by electron microscopy, FT-IR spectroscopy, X-ray diffraction, entrapment efficiency, cytotoxicity and in vivo studies. FDA-approved GEM was loaded to the purified (GEM-NT) and GEM/FA-NT, and % entrapment efficiency was found to be approximately 71.60 ± 0.25 and 79.60 ± 0.45, respectively. The developed formulation GEM/FA-NT was found to have significantly less hemolytic toxicity (8.23 ± 0.65) as compared to free GEM (17.34 ± 0.56). The in vitro release was found to be in sustained pattern at the lysosomal pH, which depicts more cytotoxic response on human breast cancer cell line (MCF-7). It may be interpreted that the GEM/FA-NT formulation is capable to carry drug and deliver it selectively at the tumor site while minimizing side effects and thus holds promise in chemotherapy.
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Tagging the expressed protein with 6 histidines: rapid cloning of an amplicon with three options.
PLoS ONE
PUBLISHED: 01-01-2013
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We report the designing of three expression vectors that can be used for rapid cloning of any blunt-end DNA segment. Only a single set of oligonucleotides are required to perform the amplification of the target DNA and its cloning in all three vectors simultaneously. The DNA thus cloned can express a protein either with or without a hexa-histidine tag depending upon the vector used. The expression occurs from T7 promoter when transformed into E. coli BL21(DE3). Two of the three plasmids have been designed to provide the expressed protein with either N- or C-terminus 6 histidine amino acids in tandem. The third plasmid, however, does not add any tag to the expressed protein. The cloning is achieved quickly with the requirement of phosphorylation of PCR product without any restriction digestion. Additionally, the generated clones can be confirmed with a single step PCR reaction carried out from bacterial colonies (generally termed as "colony PCR"). We show the cloning, expression and purification of Green Fluorescent Protein (GFP) as proof-of-concept. Additionally, we also show the cloning and expression of four sigma factors from Mycobacterium tuberculosis further demonstrating the utility of the designed plasmids. We strongly believe that the vectors and the strategy that we have developed will facilitate the rapid cloning and expression of any gene in E. coli BL21(DE3) with or without a hexa-histidine tag.
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Compositional control of higher order assembly using synthetic collagen peptides.
J. Am. Chem. Soc.
PUBLISHED: 12-21-2011
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We present the case of a two-component collagen peptide hydrogel that self-assembles through noncovalent electrostatic interactions. Natural collagen materials, such as those of connective tissue or the basement membrane, assemble in a hierarchic fashion. Similarly, the synthetic peptides presented here proceed from monomer to trimer to fiber and, finally, to a hydrogel. By varying stoichiometry and concentration, we are able to dissect the stages of higher order assembly. Insight gained from this study will improve the molecular design of biomimetic materials.
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Crystal structure of the bacteriophage T4 late-transcription coactivator gp33 with the ?-subunit flap domain of Escherichia coli RNA polymerase.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-01-2011
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Activated transcription of the bacteriophage T4 late genes, which is coupled to concurrent DNA replication, is accomplished by an initiation complex containing the host RNA polymerase associated with two phage-encoded proteins, gp55 (the basal promoter specificity factor) and gp33 (the coactivator), as well as the DNA-mounted sliding-clamp processivity factor of the phage T4 replisome (gp45, the activator). We have determined the 3.0 ?-resolution X-ray crystal structure of gp33 complexed with its RNA polymerase binding determinant, the ?-flap domain. Like domain 4 of the promoter specificity ? factor (?(4)), gp33 interacts with RNA polymerase primarily by clamping onto the helix at the tip of the ?-flap domain. Nevertheless, gp33 and ?(4) are not structurally related. The gp33/?-flap structure, combined with biochemical, biophysical, and structural information, allows us to generate a structural model of the T4 late promoter initiation complex. The model predicts protein/protein interactions within the complex that explain the presence of conserved patches of surface-exposed residues on gp33, and provides a structural framework for interpreting and designing future experiments to functionally characterize the complex.
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Factorial design-based development of measlamine microspheres for colonic delivery.
Biomatter
PUBLISHED: 10-01-2011
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For treating colonic diseases, conventional oral drug delivery systems are not effective, as they fail to reach the appropriate site of action. Thus, there is a need to develop effective and safe therapy for the treatment of colonic disorders. The aim of the present study was to design a colon-specific delivery system for an anti-inflammatory drug, mesalamine, with minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Factorial designs (four factors and two levels) for eudragit S-100 (pH-dependent polymer)-coated, pectin (natural polysaccharides)-based microspheres of mesalamine were constructed and conducted in a fully randomized manner to study all possible combinations. Based on the desirability function formulation, F14 was found to be the best formulation. The overall desirability coefficient of formulation F14 was found to be 0.825. The formulation F14 was subjected to in vitro release studies, and the results were evaluated kinetically and statistically. The microspheres started releasing the drug at the beginning of 7th hour, which corresponds to the arrival time at proximal colon. The cumulative percent drug release for formulation F14 at the end of 16 h was found to be 98%. The release kinetics showed that the release followed the Higuchi model, and the main mechanism of drug release was diffusion. The study presents a new approach for colon-specific drug delivery.
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Recent technologies in pulsatile drug delivery systems.
Biomatter
PUBLISHED: 07-01-2011
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Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as Pulsincap™, Diffucaps(®), CODAS(®), OROS(®) and PULSYS™, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases.
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Design and characterization of colon-specific drug delivery system containing paracetamol microsponges.
Arch. Pharm. Res.
PUBLISHED: 06-09-2011
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The present work was aimed at designing microsponge based colon specific drug delivery system containing paracetamol. Eudragit S-100 based microsponges containing drug in varying amounts were prepared using quasi-emulsion solvent diffusion method. The microsponges were prepared by optimizing various process parameters. DSC and FTIR studies indicated compatibility of the drug in various formulations. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies and the results were evaluated kinetically and statistically. The in vitro release data showed a bi-phasic pattern with an initial burst effect. In the first hour drug release from microsponges was found to be between 18-30%. The cumulative percent release at the end of 12(th) hour was noted to be between 74-98%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion. The colon specific tablets were prepared by compressing the microsponges followed by coating with pectin: hydroxypropylmethyl cellulose (HPMC) mixture. In vitro release studies exhibited that compression coated colon specific tablet formulations started releasing the drug at 6(th) hour corresponding to the arrival time at proximal colon. The study presents a new approach for colon specific drug delivery.
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Development and characterization of dutasteride bearing liposomal systems for topical use.
Curr Drug Discov Technol
PUBLISHED: 04-15-2011
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Dutasteride loaded liposomal system were developed for topical application in order to avoid the side effects associated with the oral administration of the drug. Drug-loaded multilamellar liposomes were prepared using thin-film hydration method followed by sonication and optimized with respect to entrapment efficiency, drug payload, size and lamellarity. The vesicular systems consisting of egg phosphatidylcholine (100 mg), cholesterol (50 mg), and dutasteride (5 mg) showed highest drug entrapment efficiency (94.6%) and drug payload (31.5 µg/mg of total lipids). Mean vesicle size of these liposomes was noted to be 1.82 ± 0.15 µm. Significantly higher skin permeation of dutasteride through excised abdominal mouse skin was achieved via the developed liposomal formulations as compared to hydro-alcoholic solution and conventional gels. The formulation exhibited about seven fold higher deposition of drug in skin. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 10 weeks with negligible drug leakage or vesicle size alteration. Results of the current studies exhibited improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.
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Development and characterization of mucoadhesive nanosuspension of ciprofloxacin.
Acta Pol Pharm
PUBLISHED: 04-13-2011
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Mucoadhesive nanosuspension of ciprofloxacin was designed in order to improve the solubility, bioavailability and efficacy for the treatment of typhoid fever. The identity and purity of drug was established. The compatibility of drug with various excipients was ascertained by FTIR techniques, which indicated no interaction between the drug and excipients. Four different formulations were prepared by optimizing various parameters using different polymers like soya lecithin, pluronic F68, polyvinyl alcohol, and polyvinylpyrrolidone K30. Particle size and polydispersity index were determined by photon correlation spectroscopy. Average particle size of different formulations was found to be between 503-1844 nm. The zeta potential of all formulations was found to be around +/- 20 My indicating satisfactory physical stability. Scanning electron microscopy showed that process parameters affect the crystal morphology. The promising formulations prepared from combination of soya lecithin and pluronic F68 and those based on soya lecithin alone were subjected to dissolution profile studies. The later formulation exhibited fast dissolution rate as compared to the former. Thus nanosus-pension based on soya lecithin was incorporated into hydrogels prepared using different grades of carbopol 934 and 971 as mucoadhesive polymers. After 10 h, mucoadhesive nanosuspensions showed 45-56% release. The developed mucoadhesive nanosuspensions exhibited satisfactory physical stability. The studies indicated potential of these formulations as novel gastroretentive systems.
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Ciprofloxacin surf-plexes in sub-micron emulsions: a novel approach to improve payload efficiency and antimicrobial efficacy.
Int J Pharm
PUBLISHED: 02-14-2011
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The aim of this study was to investigate antimicrobial efficacy and pharmacokinetic profile of ciprofloxacin (CFn) loaded oil-in-water (o/w) submicron emulsion (SE-CFn). This study emphasized on development of hydrophobic ion-pair complexes of CFn with sodium deoxycholate (SDC) [CFn-SDC], which was incorporated in the core of SE (SE-CFn-SDC). SE-CFn-SDC was characterized for globulet size (278±12 nm), zeta potential (-25.3±1 mV), viscosity (2.6±0.3 cP), transmission electron microscopy (TEM), drug entrapment and for in vitro release profile. The entrapment efficiency (EE) was significantly improved (?80%; p?0.05) on ion-pairing while it was merely 27.2±3.1% for free CFn. The cytotoxicity studies of formulations on J774 macrophage cells showed that more than 90±3% of cells were viable, even at high concentration (100 ?g/ml). SE-CFn-SDC was further modified with cationic inducer chitosan (SE-CH-CFn-SDC), which showed almost twofold and fourfold enhancement in antimicrobial efficacy as compared to SE-CFn-SDC and SE-CFn, respectively when tested in vitro against E. coli, S. aureus, and P. aeruginosa. When tested in male Balb/c mice, the AUC(0-24h) of SE-CH-CFn-SDC (23.27±2.8 h ?g/ml) was found to be 1.7-fold and 5-fold higher as compared to SE-CFn-SDC (13.17±0.88 h ?g/ml) and CFn solution (4.70±0.77 h ?g/ml), respectively. The study demonstrates that surfactant based ionic complex formation incorporated in surface modified submicron emulsion is a promising approach to improve payload efficiency of poorly water soluble drugs with improved antimicrobial efficacy and pharmacokinetic profile.
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Coupled folding and specific binding: fishing for amphiphilicity.
Int J Mol Sci
PUBLISHED: 01-25-2011
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Proteins are uniquely capable of identifying targets with unparalleled selectivity, but, in addition to the precision of the binding phenomenon, nature has the ability to find its targets exceptionally quickly. Transcription factors for instance can bind to a specific sequence of nucleic acids from a soup of similar, but not identical DNA strands, on a timescale of seconds. This is only possible with the enhanced kinetics provided for by a natively disordered structure, where protein folding and binding are cooperative processes. The secondary structures of many proteins are disordered under physiological conditions. Subsequently, the disordered structures fold into ordered structures only when they bind to their specific targets. Induced folding of the protein has two key biological advantages. First, flexible unstructured domains can result in an intrinsic plasticity that allows them to accommodate targets of various size and shape. And, second, the dynamics of this folding process can result in enhanced binding kinetics. Several groups have hypothesized the acceleration of binding kinetics is due to induced folding where a "fly-casting" effect has been shown to break the diffusion-limited rate of binding. This review describes experimental results in rationally designed peptide systems where the folding is coupled to amphiphilicity and biomolecular activity.
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Comparison of humoral and cell-mediated immune responses to cationic PLGA microspheres containing recombinant hepatitis B antigen.
Int J Pharm
PUBLISHED: 01-21-2011
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Presently available marketed alum adsorbed hepatitis B vaccine used for prophylactic immunization, can effectively elicit humoral immunity but is poor inducer of cell-mediated immunity (CMI). Besides, conventional alum-adjuvant vaccines require multiple injections to achieve long-lasting protective immune responses. Therefore, as a result of insufficient immunization, infections are still the leading killer among diseases. The present investigation was therefore, aimed at developing "single-shot" HBsAg adsorbed microspheres of poly (DL)-lactide-co-glycolide (PLGA) (L/G 50:50 and 75:25) and their capability to stimulate the cell mediated immune response against hepatitis B surface antigen. These microspheres were characterized in vitro for their size, shape polydispersity index, percentage HBsAg adsorption efficiency and in vitro release profile. The immune-stimulating activities were also studied following subcutaneous injection of HBsAg adsorbed PLGA microspheres (single-dose on day 0) and compared with alum adsorbed vaccines (two-doses on 0 and 28 days) in Balb/c mice. Specific cell-mediated immune responses such as lymphocyte transformation assay (stimulation-index) including release of interferon-gamma (IFN-?), interleukin-2 (IL-2) and nitric-oxide were determined. Cellular responses in case of alum adsorb HBsAg vaccine was very low. These studies demonstrate the potential of cationic polymeric microspheres based vaccine in stimulating cell mediated immune response along with humoral response against hepatitis B.
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Templated ultrathin polyelectrolyte microreservoir for delivery of bovine serum albumin: fabrication and performance evaluation.
AAPS PharmSciTech
PUBLISHED: 01-19-2011
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The aim of the study was to develop ultrathin polyelectrolyte microreservoir (UPM) using two combinations of synthetic/synthetic (S/s; poly(allylamine hydrochloride) (PAH)/sodium poly(styrenesulfonate)) and synthetic/natural (S/n; PAH/sodium alginate) polyelectrolytes over spherical porous CaCO(3) core particles (CP) followed by core removal and to evaluate its biocompatibility and integrity of loaded model protein bovine serum albumin (BSA). A novel process for synthesis of CP was developed to obtain maximum yield of monodisperse vaterite (spherical) polymorph. The prepared UPM was characterized for surface morphology, layer-by-layer growth, pay load efficiency, integrity of BSA, as well as viability and cell adhesion using murine J 774 macrophages (?). In vitro release profile revealed that both S/s and S/n UPM were able to provide sufficient diffusion barrier to release protein at physiological pH. It has been observed that S/n UPM are fully biocompatible due to obvious reason of using natural polymer. In a separate experiment, the S/s UPM surface was modified with pluronic F-68 to tune biocompatibility which provides evidences for safety and tolerability of the S/s UPM as well. In nutshell, the proposed system could successfully be used for the delivery of proteins, and moreover, the system can be tailored to impart desired properties at any stage of layering especially in terms of drug release and to retain the integrity of proteins.
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Primary diffuse large B-cell lymphoma of the skull mimicking osteomyelitis.
Ear Nose Throat J
PUBLISHED: 01-14-2011
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Primary lymphomas of the skull are extremely rare, as fewer than 20 cases have been reported in the literature. We describe the case of a 51-year-old woman with Huntington chorea who presented with forehead swelling. Imaging studies detected an enhancing mass in the skull with some destruction of the underlying bone. These features were suggestive of osteomyelitis. Surgical excision was performed, and the mass was found to be a primary diffuse large B-cell lymphoma. The patient was administered postoperative chemotherapy, and she was in complete remission at the 1-year follow-up.
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Microporous bilayer osmotic tablet for colon-specific delivery.
Eur J Pharm Biopharm
PUBLISHED: 01-01-2011
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Microporous bilayer osmotic tablet bearing dicyclomine hydrochloride and diclofenac potassium was developed using a new oral drug delivery system for colon targeting. The tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan-coating process. The developed microporous bilayer osmotic pump tablet (OPT) did not require laser drilling to form the drug delivery orifice. The colon-specific biodegradation of pectin could form in situ delivery pores for drug release. The effect of formulation variables like inclusion of osmogen, amount of HPMC and NaCMC in core, amount of pore former in semipermeable membrane was studied. Scanning electron microscopic photographs showed formation of in situ delivery pores after predetermined time of coming in contact with dissolution medium. The number of pores was dependent on the amount of the pore former in the semipermeable membrane. In vitro dissolution results indicated that system showed acid-resistant, timed release and was able to deliver drug at an approximate zero order up to 24h. The developed tablets could be effectively used for colon-specific drug delivery to treat IBS.
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Donor gonadal vein reconstruction for extension of the transected renal vessels in living renal transplantation.
Indian J Urol
PUBLISHED: 09-30-2010
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Donor gonadal vein is a readily available vascular reconstruction material for vascular reconstruction, for difficult situations, in living related renal transplantation. Vein extension with the gonadal vein has been described as a simple and safe method to elongate renal vein especially in right living donor kidneys. We applied the donor gonadal vein for lacerated accessory renal artery and renal vein reconstruction.
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Factors effecting the morphology of eudragit S-100 based microsponges bearing dicyclomine for colonic delivery.
J Pharm Sci
PUBLISHED: 07-24-2010
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The purpose of this study was to design microsponge-based novel colon-specific drug delivery system bearing dicyclomine. Eudragit S-100-based microsponges containing the drug in varying amount were prepared using quasi-emulsion solvent diffusion method. The microsponges were prepared by optimizing various process parameters. Differential scanning calorimetry and Fourier transform infrared studies indicated compatibility and stability of the drug in various formulations. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies, and the results were evaluated kinetically and statistically. In vitro release data showed a biphasic pattern with an initial burst effect. In the first hour, drug release from microsponges was found to be between 17% and 31%. The cumulative percent release at the end of eighth hour was noted to be between 53% and 83%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion. The colon-specific tablets were prepared by compressing the microsponges followed by coating with pectin:hydroxypropylmethylcellulose mixture. In vitro release studies exhibited that compression-coated colon-specific formulations started releasing the drug at the sixth hour corresponding to the arrival time at colon. The study presents a new approach for colon-specific drug delivery. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1545-1552, 2011.
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Development and characterization of eudragit RS 100 loaded microsponges and its colonic delivery using natural polysaccharides.
Acta Pol Pharm
PUBLISHED: 07-20-2010
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In the present work, paracetamol loaded eudragit based microsponges were prepared using quasi-emulsion solvent diffusion method. The compatibility of the drug with various formulation components was established. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies and the results were evaluated kinetically and statically. The in vitro release data showed a bi-phasic pattern with an initial burst effect. In the first hour drug release from microsponges was found to be between 17-30%. The cumulative percent release at the end of 8th hour was noted to be between 54-83%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion.The colon specific tablets were prepared by compressing the microsponges followed by coating with pectin:hydroxypropylmethylcellulose (HPMC) mixture. In vitro release studies exhibited that compression coated colon specific tablet formulations started releasing the drug at 6th hour corresponding to the arrival time at proximal colon. The study presents a new approach for colon specific drug delivery.
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Urological manifestations of Chikungunya fever: A single centre experience.
Urol Ann
PUBLISHED: 05-24-2010
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Chikungunya is a viral infection often associated with lower urinary tract dysfunction. This study evaluates the urological squeal of Chikungunya fever in a single centre after an epidemic in 2006-2007 in India.
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Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes.
Nanomedicine
PUBLISHED: 01-03-2010
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Indinavir, as a protease inhibitor with a short biological half life, variable pH-dependent oral absorption, and extensive first-pass metabolism, presents a challenge with respect to its oral administration. The current work aims to formulate and characterize indinavir-bearing ethanolic liposomes (ethosomes), and to investigate their enhanced transdermal delivery potential. The prepared ethanolic liposomes were characterized to be spherical, unilamellar structures having low polydispersity, nanometric size range, and improved entrapment efficiency over other delivery formulations. Permeation studies of indinavir across human cadaver skin resulted in enhanced transdermal flux from ethanolic liposomes that was significantly (P < 0.05) greater than that with ethanolic drug solution, conventional liposomes, or plain drug solution. Additionally, the ethanolic liposomes showed the shortest lag time for indinavir, thus presenting a suitable approach for transdermal delivery of this protease inhibitor. From the clinical editor: This study characterizes indinavir bearing ethanolic liposomes (ethosomes), and investigate their enhanced transdermal delivery potential, demonstrating a potentially a suitable approach for transdermal delivery of this protease inhibitor for HIV treatment, which typically has been associated with limited bioavailability via the oral route.
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Management of non-neoplastic renal hemorrhage by transarterial embolization.
Urology
PUBLISHED: 07-09-2009
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To assess the role of transarterial embolization (TAE) and critically appraise its feasibility and efficacy in the management of non-neoplastic renal hemorrhage. Percutaneous TAE is an effective method for the control of hemorrhage, irrespective of the cause. Injury to the renal artery or its branch, after trauma or during open or percutaneous urologic procedures, can be accurately diagnosed using angiography and treated by percutaneous embolization techniques. Because the technique and technology have evolved, it is now possible to perform highly selective embolization of the injured vessel while preserving vascularity of the rest of the renal parenchyma.
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Development and characterization of lectin-functionalized vesicular constructs bearing amphotericin B for bio-film targeting.
J Drug Target
PUBLISHED: 04-18-2009
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The long-term goal of this work will be to develop a topical formulation for oropharyngeal candidosis. Liposomes were prepared by the vesicle extrusion technique from mixtures of dipalmitoylphosphatidylcholine, cholesterol, and stearylamine incorporating a reactive phospholipid, the m-maleimidobenzoyl-N-hydroxysuccinimide ester derivative of dipalmitoylphosphatidylethanolamine, which was conjugated with the N-succinimidyl-S-acetylthioacetate derivatives of succinyl concanavalin A. Morphology of liposomes was studied by transmission electron microscopy and bio-film architecture using fluorescence microscopy. Lectinized vesicles were put into contact with bovine submaxillary mucin, to determine the in vitro activity and specificity. Targeting study was performed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The liposomes were found to have a diameter in the range of 360-450 and 390-510 nm for uncoated and coated formulations, respectively. The MTT assay showed a strong association of lectin-bearing liposomes with candidal bio-film. The results suggest that surface-modified liposomes can effectively target candidal bio-film in vitro.
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Pacemaker induced superior vena cava syndrome: a case report.
Cases J
PUBLISHED: 03-06-2009
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Pacemaker induced superior vena cava syndrome is an unusual complication of pacemaker implantation. Endothelial damage caused by repeated trauma from the lead is thought to be responsible for the stenosis. Malignancy has been historically the most common etiology. However, the increase in use of indwelling venous catheters and cardiac pacemaker has resulted in more patients with superior vena cava syndrome of benign etiology.
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Galactose-grafted chylomicron-mimicking emulsion: evaluation of specificity against HepG-2 and MCF-7 cell lines.
J. Pharm. Pharmacol.
PUBLISHED: 02-19-2009
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A chylomicron-mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel-CM) and was further grafted with galactose (paclitaxel-GCM) using palmitoyl-galactosamine, which was synthesized by reacting galactosamine hydrochloride with N-hydroxy succinimide ester of palmitic acid. Palmitoyl-galactosamine was used as a ligand for asialoglycoprotein receptors.
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Laparoscopic pyeloplasty: our new gold standard.
J. Endourol.
PUBLISHED: 02-06-2009
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Laparoscopic pyeloplasty has developed as a successful minimally invasive alternative to open surgery for management of ureteropelvic junction obstruction (UPJO). Reported medium-term success rates match those of open surgery at more than 90%. We present our complete experience to date with the laparoscopic pyeloplasty procedure.
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Well-defined and potent liposomal hepatitis B vaccines adjuvanted with lipophilic MDP derivatives.
Nanomedicine
PUBLISHED: 01-19-2009
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The characterization of immunological cascades of the innate immune system activated by invariant molecular structures termed as pathogen-associated molecular patterns recognized by pattern recognition receptors of macrophages and dendritic cells, have allowed the elucidation of the mechanisms underlying the immunomodulatory properties of adjuvants. Thus, adjuvant-active lipophilic analogues of N-acetyl muramyl dipeptide (MDP) were incorporated in liposomal hepatitis B surface antigen (HBsAg) formulations. The immunoreactivity of the formulations was evaluated by measuring anti-HBs, immunoglobulin G (IgG), and isotype antibody titer and compared with alum-adsorbed HBsAg formulation. The formulations were also evaluated for cell-mediated immune response by HBsAg-specific proliferation of splenocytes and simultaneous estimation of cytokines (interleukin-4 [IL-4], interferon-gamma [IFN-gamma]). Results indicate that the serum IgG and anti-HBs titer obtained after intramuscular administration of liposomal muramyl tripeptide-phosphatidylethanolamine (MTP-PE) and liposomal N-acetylmuramyl-l-alanyl-d-isoglutamine-glycerol dipalmitate (MDP-GDP) antigenic formulations were significantly higher. The incorporation of MTP-PE on the liposomal HBsAg increased the stimulation index (SI) four to five times as compared to plain HBsAg solution, and it also induced significantly higher Th1 cellular immune response with a predominant IFN-gamma level. So it is the novel effective and potentially safe approach in which liposomes act as delivery vehicles for hepatitis B viral antigen to antigen-presenting cells and is ornamented with a biological response modifier that could activate these target cells to enhance the antigen presentation to T lymphocytes.
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Modeling the dynamic folding and surface-activity of a helical peptide adsorbing to a pendant bubble interface.
J Colloid Interface Sci
PUBLISHED: 01-10-2009
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We have designed a peptide with switchable surface activity, where the folded (alpha-helical) form of the peptide is amphiphilic and the unfolded form is not. To understand the factors influencing the dynamics of the switchability, a model is developed for the transport of the surface active form of the peptide from the solution onto air-water interface. As is the case with the low molecular weight head-tail surfactants, the transport involves the bulk diffusion of the folded form to the surface and the kinetic adsorption onto the interface. Unlike the head-tail surfactants, the diffusion can be augmented by the kinetics of the folding of the peptide from the unfolded form. The model is formulated within the context of the transport of the peptide from a uniform bulk solution onto an initially clean air-water interface in a pendant bubble system, where the transport rate can be measured by recording the reduction in surface tension using the shape analysis of the bubble. Experiments are undertaken and compared to the predictions of the model simulations of the tension reduction for a range of values of the kinetic adsorption constant and the folding kinetic constant. The results indicate that the kinetic adsorption rate of the folded peptide onto air-water interface dominates the dynamic process, which contrasts many head-tail surfactants where diffusion typically dominates over kinetics adsorption. Moreover, our best-fits suggest that there is a phase transition at high surface concentrations that slows the long-time adsorption of the peptides to the interface. Finally, the numerical solution is compared with an asymptotic solution, showing agreement with our findings that the fundamental dynamics of the tunable surface-active peptide are indeed controlled by the adsorption step.
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Traumatic bilateral basal ganglia hematoma: A report of two cases.
Asian J Neurosurg
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Traumatic Basal ganglia hemorrhage is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage, and review the literature in brief. Both cases were managed conservatively.
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Organochlorine pesticide residues in maternal blood, cord blood, placenta, and breastmilk and their relation to birth size.
Chemosphere
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There is a growing concern that persistent organic pollutants like organochlorine pesticides (OCPs) can impair fetal growth and affect birth size. However, currently available epidemiological evidence is inconclusive. In this case-control study, we examined the association between exposure to hexachlorocyclohexane (HCH) and its isomers (?-HCH, ?-HCH and ?-HCH), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and birth size. We recruited 60 infant-mother pairs, comprising of 30 term, small for gestational age babies with their mothers (Case group), and another 30 term, appropriate for gestational age babies with their mothers (Control group). This study was conducted in a tertiary hospital in Delhi, India, between March, 2009 and February 2010. Organochlorine pesticides were estimated in maternal blood, cord blood, placenta and breastmilk samples, using gas-liquid chromatography. Transplacental and transmammary transfer of OCPs was assessed by correlating the maternal blood OCP levels with those in cord blood and breastmilk by simple linear regression. The birthweight, crown heel length, head circumference, mid-arm circumference and ponderal index of the neonates was correlated with OCP levels in the maternal blood, cord blood, placenta and breastmilk. The OCP estimates were compared between samples of the case and control group. There was a significant (P<0.001) transplacental transfer of all OCPs, however the transmammary transfer was insignificant for most OCPs except ?-HCH. The OCP levels in the case group were higher than the control group; these were significantly more for t-HCH in cord blood and breastmilk; ?-HCH in maternal blood, cord blood and breastmilk; DDE in placenta and DDT in breastmilk. There was a significant negative correlation between birthweight and t-HCH levels in maternal blood (P=0.022), cord blood (P<0.001), placenta (P=0.008) and breastmilk (P=0.005); ?-HCH in cord blood (P<0.001) and placenta (P=0.020); ?-HCH in placenta (P=0.045); and DDT (P=0.009). Length at birth had a significant negative correlation with t-HCH in cord blood (P=0.014) and breastmilk (P<0.001); ?-HCH in cord blood (P=0.016) and breastmilk (P=0.012); DDE in placenta (P=0.016); and DDT in breastmilk (P=0.006). Similarly, OCP levels were also found to be negatively correlated with head circumference, ponderal index and chest circumference in neonates. We conclude that prenatal exposure to some OCPs could impair the anthropometric development of the fetus, reducing the birthweight, length, head circumference, chest circumference and ponderal index.
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Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life, brain delivery and efficacy in glioblastoma cells.
Nanomedicine
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Noscapine crosses blood-brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3 ± 9.3-nm and 80.5 ± 8.9-nm containing 80.4 ± 3.2% and 83.6 ± 1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH~4.5. Further, a decrease in IC?? (Nos; 40.5 ?M>Nos-SLN; 27.2 ?M>20.8 ?M) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~11-fold and ~5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P<0.05) deposits 400.7 ?g/g and 313.1 ?g/g of Nos in comparison to 233.2 ?g/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer.
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The misapplication of the term spinal cord injury without radiographic abnormality (SCIWORA) in adults.
J Trauma Acute Care Surg
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Spinal cord injury without radiographic abnormality (SCIWORA) is generally considered a disease of children; however, it is commonly used when referring to adults who have spinal cord injury without computed tomography evidence of trauma (SCIWOCTET). The purpose of this study was to describe characteristics of patients with both adult and pediatric cervical SCIWOCTET admitted to hospitals in our region.
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Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy.
Biomaterials
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A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2 ± 2.5% in 24 h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3 ± 10.2 to 4.4 ± 1.3%) and control the release of PTX (43.6 ± 3.2% released in 24 h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using (99m)Tc-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24 h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel.
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