DEVELOPMENT AND EVALUATION OF VANCOMYCIN-BERBERINE CO-LOADED/MULTILAYERED LIPOSOMES FOR THE ORAL TREATMENT OF CLOSTRIDIOIDS DIFFICILE INDUCED COLITIS

Background: The current treatment strategies against Clostridioides difficile-induced colitis have severe side effects due to the non-specific distribution of drugs throughout the body. Objectives: This study introduces a novel pH-responsive, charge-reversal multilayer liposomal system combining vancomycin (VM) and berberine (BR) to achieve synergistic therapy and selective colon targeting. Methodology: Multilayered liposomes were prepared via electrostatic layer-by-layer deposition of positively charged glycol chitosan (GC) and negatively charged Eudragit S100 (ES), protecting in gastric conditions and pH-triggered charge reversal for targeted colonic drug release, followed by in vivo evaluation in a BALB/c mouse model of C. difficile–induced colitis. Results: The optimized Eudragit S100-Glycol chitosan-liposomes (ES-GC-LP) had an average vesicle size of 130.3 ±2.1 nm and a high entrapment efficiency of 71.2 ±3.6% with respect to VM. An in vivo study showed a ~60% reduction in the disease activity index compared with untreated infected controls, with marked improvement in biocompatibility and the absence of colonic inflammation when treated with ES-GC-LP. Conclusion: ES-GC-LP could be an effective oral treatment option for C. difficile-induced colitis.