Preparation, Characterization, and Preclinical Efficacy of In Situ Gels Containing Benzydamine Hydrochloride for Oral Mucositis

Oral mucositis occurs after chemo/radiotherapy and can significantly impact patients' quality of life. The objective of this study was to develop and characterize mucoadhesive in situ gels (ISGs) using chitosan (CS) in conjunction with polymers like poloxamer (PLX) and beta-glycerophosphate (βGP) to deliver benzydamine hydrochloride (BNZ) locally. CS/PLX (2.5:20)-BNZ and CS/βGP (2:35)-BNZ were selected based on appropriate gelling temperature/time, appearance, and viscosity. These formulations released 23% and 27% of their drug content during the first 4 h and 30% and 39% during 8 h, respectively. Compared to CS/PLX (2.5:20)-BNZ, CS/βGP (2:35)-BNZ required more force to be injected in the syringeability test and showed less spreadability. G' related to both ISGs was higher than G″, which indicated an increase in gel consistency and stability at the site of action. The mucoadhesion strength of both ISGs was 10-13 g. FTIR data revealed chemical interactions between polymers but no interaction with BNZ. The antimicrobial effectiveness of ISGs loaded with BNZ was more significant than drug-free ones. In vivo evaluation showed CS/PLX (2.5:20)-BNZ significantly decreased the macroscopic and histopathological features of oral mucositis. In summary, CS/PLX (2.5:20)-BNZ exhibited satisfactory characteristics, suggesting it could be a viable local drug delivery system for oral mucositis.