phase-change-dimethyldioctadecylammonium-shelled-microdroplets-as

Phase Change Dimethyldioctadecylammonium-Shelled Microdroplets as a Promising Drug Delivery System: Results on 3D Spheroids of Mammalian Tumor Cells

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs ...

University of Rome Tor Vergata

Recently, scientific and technological interest in the synthesis of novel peptide-based hydrogel materials have grown dramatically. Applications of such materials mostly concern the biomedical field with examples covering sectors such as drug delivery, tissue engineering, and production of scaffolds for cell growth, thanks to their biocompatibility and biodegradability. In this work we synthesized Fmoc-Phe₃ based hydrogels of different chirality by using a biocatalytic approach. Moreover, we investigated the possibility of employing a crosslinker during the biosynthetic process and we studied and compared some chemico-physical features of both crosslinked and non-crosslinked hydrogels. In particular, we investigated the rheological properties of such materials, as well as their swelling ability, stability in aqueous medium, and their structure by SEM and AFM analysis. Crosslinked and non-crosslinked hydrogels could be formed by this procedure with comparable yields but distinct chemico-physical features. We entrapped dexamethasone within nanopolymeric particles based on PLGA coated or not with chitosan and we embedded these nanoparticles into the hydrogels. Dexamethasone release from such a nanopolymer/hydrogel system was controlled and sustained and dependent on genipin crosslinking degree. The possibility of efficiently coupling a drug delivery system to hydrogel materials seem particularly promising for tissue engineering applications, where the hydrogel could provide cells the necessary support for their growth, while nanoparticles could favor cell growth or differentiation by providing them the necessary bioactive molecules.

Biosynthesis and Characterization of Cross-Linked Fmoc Peptide-Based Hydrogels for Drug Delivery Applications.

Phase change contrast agents for ultrasound (US) imaging consist of nanodroplets (NDs) with a perfluorocarbon (PFC) liquid core stabilized with a lipid or a polymer shell. Liquid ↔ gas transition, occurring in the core, can be triggered by US to produce acoustically active microbubbles (MBs) in a process named acoustic droplet vaporization (ADV). MB shells containing polymerized diacetylene moiety were considered as a good trade off between the lipid MBs, showing optimal attenuation, and the polymeric ones, displaying enhanced stability. This work reports on novel perfluoropentane and perfluorobutane NDs stabilized with a monolayer of an amphiphilic fatty acid, i.e. 10,12-pentacosadiynoic acid (PCDA), cured with ultraviolet (UV) irradiation. The photopolymerization of the diacetylene groups, evidenced by the appearance of a blue color due to the conjugation of ene-yne sequences, exhibits a chromatic transition from the nonfluorescent blue color to a fluorescent red color when the NDs are heated or the pH of the suspension is basic. An estimate of the molecular weights reached by the polymerized PCDA in the shell, poly(PCDA), has been obtained using gel permeation chromatography and MALDI-TOF mass spectrometry. The poly(PCDA)/PFC NDs show good biocompatibility with fibroblast cells. ADV efficiency and acoustic properties before and after the transition were tested using a 1 MHz probe, revealing a resonance frequency between 1 and 2 MHz similar to other lipidic MBs. The surface of PCDA shelled NDs can be easily modified without influencing the stability and the acoustic performances of droplets. As a proof of concept we report on the conjugation of cyclic RGD and PEG chains of the particles to support targeting ability toward endothelial cells.

Phase Change Ultrasound Contrast Agents with a Photopolymerized Diacetylene Shell.

Hydrogel-based cleaning of paper artworks is an increasingly widespread process in the cultural heritage field. However, the search for tuned (compatible, highly retentive and not perishable) hydrogels is a challenging open question. In this paper, a complete characterization of chemical hydrogels based on polyvinyl alcohol (PVA) crosslinked with telechelic PVA and their remarkable performances as gels for cleaning paper artworks are reported. The rheological properties, porosity, water content of these gels were determined and analyzed as a function of the components concentration during synthesis. Due mechanical and retentive properties, the reported gels are optimum candidates for paper cleaning applications. The efficacy of these PVA-based gels has been demonstrated applying them on the surface of the sheets of several paper artworks, and characterizing the samples before and after the cleaning process by means of a multidisciplinary approach involving spectroscopic and chromatographic tests.

Polyvinyl alcohol based hydrogels as new tunable materials for application in the cultural heritage field.

Poly(N-isopropylacrylamide) (PNIPAM) hydrogel microparticles with different core-shell morphologies have been designed, while maintaining an unvaried chemical composition: a morphology with (i) an un-crosslinked core with a crosslinked shell of PNIPAM chains and (ii) PNIPAM chains crosslinked to form the core with a shell consisting of tethered un-crosslinked PNIPAM chains to the core. Both morphologies with two different degrees of crosslinking have been assessed by confocal microscopy and tested with respect to their temperature responsivity and deformation by applying an osmotic stress. The thermal and mechanical behavior of these architectures have been framed within a Flory-Rehner modified model in order to describe the microgel volume shrinking occurring as response to a temperature increase or an osmotic perturbation. This study provides a background for assessing to what extent the mechanical features of the microgel particle surface affect the interactions occurring at the interface of a microgel particle with a cell, in addition to the already know ligand/receptor interaction. These results have direct implications in triggering a limited phagocytosis of microdevices designed as injectable drug delivery systems.

Microgel Particles with Distinct Morphologies and Common Chemical Compositions: a Unified Description of the Responsivity to Temperature and Osmotic Stress.

Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase-change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation-induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons.

Article	Year
Biosynthesis and Characterization of Cross-Linked Fmoc Peptide-Based Hydrogels for Drug Delivery Applications. Gels (Basel, Switzerland)\| PubMed ID: 30674172	2015
Phase Change Ultrasound Contrast Agents with a Photopolymerized Diacetylene Shell. Langmuir : the ACS journal of surfaces and colloids\| PubMed ID: 31042396	2019
Polyvinyl alcohol based hydrogels as new tunable materials for application in the cultural heritage field. Colloids and surfaces. B, Biointerfaces\| PubMed ID: 32004905	2020
Microgel Particles with Distinct Morphologies and Common Chemical Compositions: a Unified Description of the Responsivity to Temperature and Osmotic Stress. Gels (Basel, Switzerland)\| PubMed ID: 33081416	2020
Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat. Medical physics\| PubMed ID: 33587754	2021

Yosra Toumia

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