Preparation and Characterization of Biopolymeric-Based Orally Dissolving Mucoadhesive Hydrogels Loaded With Rosuvastatin for the Effective Treatment of Aphthous Ulcer.

Abstract

The primary objective of this study was to develop and evaluate a sustained-release mucoadhesive hydrogel loaded with Rosuvastatin (RSV) to enhance the treatment of aphthous ulcers. By leveraging the pleiotropic anti-inflammatory and tissue-repair properties of RSV, the study aimed to overcome the rapid clearance and low efficacy associated with conventional oral gels and mouthwashes. Mucoadhesive hydrogels were formulated using Carbopol 934 and sodium alginate via a freeze-thaw crosslinking technique. Four formulations (F1-F4) were prepared and evaluated for morphology, swelling behavior, viscosity, mucoadhesive strength, drug entrapment efficiency, pH, in vitro drug release, antimicrobial activity, cytocompatibility, and in vivo therapeutic efficacy. Antimicrobial activity was assessed against Streptococcus mutans (ATCC 10231) and Staphylococcus aureus (MTCC 2940), while cytocompatibility was determined using an MTT assay on fibroblast cells. The formulated mucoadhesive hydrogel showed good swelling behavior, thermal stability, and controllable biodegradability. The four formulations (F1, F2, F3, and F4) exhibited significant entrapment efficiency (72.14% ± 1.5% to 95.12% ± 0.28%), and the pH was 6.7. The optimized formulation (F3) demonstrated sustained RSV release of 96.8% ± 1.4% over 8 h. We found that F3 may inhibit the growth of both Streptococcus mutans (ATCC 10231) and Staphylococcus aureus (MTCC 2940) (MRSA), which are common aphthous ulcer infectious bacteria. Cytocompatibility studies confirmed that F3 supported fibroblast viability and enhanced cell proliferation. In vivo evaluation further demonstrated improved healing of oral ulcers, supported by histopathological findings indicating enhanced tissue regeneration and reduced inflammation. The RSV-loaded mucoadhesive hydrogel (F3) exhibited high drug entrapment, sustained release, effective antimicrobial activity, and excellent biocompatibility, leading to significant therapeutic efficacy in an animal model. These findings suggest that the developed hydrogel is a promising and safe alternative for the treatment of aphthous ulcers, warranting further clinical investigation.