Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides.

Gelatin is a water-soluble natural polyampholyte with poor mucoadhesive properties. It has traditionally been used as a major ingredient in many pharmaceuticals, including soft and hard capsules, suppositories, tissue engineering, and regenerative medicine. The mucoadhesive properties of gelatin can be improved by modifying it through conjugation with specific adhesive unsaturated groups. In this study, gelatin was modified by reacting with crotonic, itaconic, and methacrylic anhydrides in varying molar ratios to yield crotonoylated-, itaconoylated-, and methacryloylated gelatins (abbreviated as Gel-CA, Gel-IA, and Gel-MA, respectively). The successful synthesis was confirmed using 1H NMR, FTIR spectroscopies, and colorimetric TNBSA assay. The effect of chemical modification on the isoelectric point was studied through viscosity and electrophoretic mobility measurements. The evolution of the storage (G') and loss (G'') moduli was employed to determine thermoreversible gelation points of modified and unmodified gelatins. The safety of modified gelatin derivatives was assessed with an in vivo slug mucosal irritation test (SMIT) and an in vitro MTT assay utilizing human pulmonary fibroblasts cell line. Two different model dosage forms, such as physical gels and spray-dried microparticles, were prepared and their mucoadhesive properties were evaluated using a flow-through technique with fluorescent detection and a tensile test with ex vivo porcine vaginal tissues and sheep nasal mucosa. Gelatins modified with unsaturated groups exhibited superior mucoadhesive properties compared to native gelatin. The enhanced ability of gelatin modified with these unsaturated functional groups is due to the formation of covalent bonds with cysteine-rich subdomains present in the mucin via thiol-ene click Michael-type addition reactions occurring under physiologically relevant conditions.

In vitro and in vivo toxicity of thiolated and PEGylated organosilica nanoparticles.

This study comprises the comprehensive toxicological assessment of thiolated organosilica nanoparticles (NPs) synthesised from 3-mercaptopropyltrimethoxysilane (MPTS). We investigated the influence of three different types of nanoparticles synthesised from 3-mercaptopropyltrimethoxysilane: the starting thiolated silica (Si-NP-SH) and their derivatives prepared by surface PEGylation with PEG 750 (Si-NP-PEG750) and 5000 Da (Si-NP-PEG5000) on biological subjects from in vitro to in vivo experiments to explore the possible applications of those nanoparticles in biomedical research. As a result of this study, we generated a comprehensive understanding of the toxicological properties of these nanoparticles, including their cytotoxicity in different cell lines, hemolytic properties, in vitro localisation, mucosal irritation properties and biodistribution in BALB/c mice. Our findings indicate that all three types of nanoparticles can be considered safe and have promising prospects for use in biomedical applications. Nanoparticles did not affect the viability of HPF, MCF7, HEK293 and A549 cell lines at low concentrations (up to 100 µg/mL); moreover, they did not cause organ damage to BALB/c mice at concentrations of 10 mg/kg. The outcomes of this study enhance our understanding of the impact of organosilica nanoparticles on health and the environment, which is vital for developing silica nanoparticle-based drug delivery systems and provides opportunities to expand the applications of organosilica nanoparticles.