Aim: This study aimed to develop nanoaggregates of berberine-phospholipid complex incorporated into thiolated chitosan (TCS) hydrogel for the treatment of aphthous stomatitis. Methods: The berberine-phospholipid complex was formulated through the solvent evaporation technique and assembled into nanoaggregates. TCS was synthesized through the attachment of thioglycolic acid to chitosan (CS). Nanoaggregates-TCS was prepared by the incorporation of nanoaggregates into TCS and underwent in vitro and in vivo tests. Results: Nanoaggregates-TCS exhibited prolonged release of berberine. The mucoadhesive strength of nanoaggregates-TCS increased 1.75-fold compared with CS hydrogel. In vivo studies revealed the superior therapeutic efficacy of nanoaggregates-TCS compared with that of other groups. Conclusion: Due to prolonged drug release, appropriate residence time and anti-inflammatory effects, nanoaggregates-TCS is an effective system for the treatment of aphthous stomatitis.
Keywords: aphthous stomatitis; berberine; hydrogel; nanoaggregates; phospholipid complex; prolonged drug delivery; thiolated chitosan.