Synthesis and Characterization of Thiolated PVP–Iodine Complexes: Key to Highly Mucoadhesive Antimicrobial Gels

Abstract

The aim of this study was to synthesize iodine containing polymeric excipients for mucosal treatment of microbial infection exhibiting a prolonged mucosal residence time by forming an adhesive gel on the mucosal surface. In order to achieve this aim, 2-(2 acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinylpyrrolidone (NVP) to obtain thiolated polyvinylpyrrolidone (PVP) for complexation with iodine. The average molecular mass of different thiolated PVP variants was determined by size exclusion chromatography. The structure of thiolated PVP was confirmed by H NMR. Thiolated PVP variants were characterized for thiol content, cytotoxicity, iodine loading capacity, rheological behavior, and adhesion time on mucosa. The highest achieved degree of thiolation was 610 ± 43 μmol/g, and the maximum recorded iodine loading was 949 ± 31 μmol/g of polymer. Thiolated PVP variants (0.5% m/v) showed no toxicity after incubation on Caco-2 cells for the period of 3 and 24 h, respectively. Thiolated PVP and thiolated PVP-iodine complexes exhibited a 5.4- and 4.4-fold increased dynamic viscosity in porcine mucus in comparison to PVP and PVP-iodine complex, respectively. Compared to PVP and PVP-iodine complex thiol-functionalized PVP and PVP-iodine complexes demonstrated significantly prolonged attachment to mucosal surface over a period of 3 h. Thiol functionalized PVP proved to be a promising novel excipient for complexation with iodine and to exhibit strongly improved mucoadhesive properties.

Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition

“…The use of PVP-iodine pre-treatment shown improved ability to prevent dental caries in vivo. Jalil et al demonstrated that the thiolated PVP and PVP-iodine complexes have shown significant mucosal adhesion for a prolonged duration of 3 h in comparison with the PVP and PVP-iodine complexes [ 168 ]. Hence, they reported that the thiol functionalized PVP is a promising novel excipient suitable for complexation with iodine to exhibit strong mucoadhesive properties.…”

Polymeric Iodophors: Preparation, Properties, and Biomedical Applications

“…PVP is a nonionic polymer and lacks a high adhesion capacity to mucous membranes [99]. To improve the mucoadhesive properties of PVP and PVP-iodine, thiolated particles were synthesized via copolymerization of N-vinylpyrrolidone with 2-(2-acryloylethyldisulfanyl)nicotinic acid [89]. The resulting thiolated particles were well capable of producing gels with pig gastric mucin in higher-viscosity conditions.…”

Silica Nanoparticles in Transmucosal Drug Delivery

“…Thiomers are a class of mucoadhesive materials which can be synthesised through the immobilisation of thiol groups on various materials. Some examples of thiomers include thiolated-polycarbophil [73], chitosan [74], pectin [75,76], graphene oxide [77], polyvinylpyrrolidone [78], and hyaluronic acid [79]. Their mucoadhesive properties can be due to their ability to form disulfide bonds with cysteine-rich domains of mucus glycoproteins via thiol/disulfide exchange reactions or oxidation of their thiol groups.…”