Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides
Shatabayeva E.O. Kaldybekov D.B. Ulmanova L. Zhaisanbayeva B.A. Mun E.A. Kenessova Z.A. Kudaibergenov S.E. Khutoryanskiy V.V.
11 March 2024American Chemical Society
Biomacromolecules
2024#25Issue 31612 - 1628 pp.
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.
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Reading School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6DX, United Kingdom
Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Institute of Polymer Materials and Technology, Almaty, 050019, Kazakhstan
School of Sciences and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan
School of Engineering and Digital Sciences, Nazarbayev University, Astana, 010000, Kazakhstan
Reading School of Pharmacy
Department of Chemistry and Chemical Technology
Institute of Polymer Materials and Technology
School of Sciences and Humanities
School of Engineering and Digital Sciences
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