Title : Mucoadhesive bigel for vaginal delivery of dolutegravir–lamivudine for HIV pre-exposure prophylaxis

Purpose: Despite advances in prevention and therapy, HIV continues to be a serious worldwide health problem, and women represent a disproportionately affected population. Vaginal microbicides offer a promising pre-exposure prophylactic strategy; however, conventional gels suffer from rapid clearance, leakage, and suboptimal retention. The present study aimed to develop and evaluate a novel mucoadhesive, vaginal bigel for the localized delivery of a fixed-dose combination of dolutegravir and lamivudine to enhance prophylactic efficacy and user compliance.

Methods: Bigels comprising a gelatin–HPMC–hyaluronic acid hydrogel and a glyceryl monostearate–olive oil organogel were prepared in varying ratios. Lamivudine was incorporated into the hydrogel phase, while dolutegravir was loaded into the organogel. Formulations were evaluated for rheology, pH, drug content, mucoadhesion, enzyme-responsive drug release in simulated vaginal and seminal fluids, cytotoxicity, apoptosis, genotoxicity, and in vivo pharmacokinetics in rabbits.

Results: The optimized formulations exhibited pseudoplastic viscoelastic behaviour, physiological pH (6.5-6.8), high drug content (>80%), and strong mucoadhesive retention for 24 h. Enzyme-responsive release demonstrated biphasic kinetics with rapid lamivudine release followed by sustained dolutegravir release over 24 h. In vitro cellular studies confirmed enhanced apoptosis in HeLa cells with minimal toxicity and no genotoxicity in normal 3T3-L1 fibroblasts. In vivo studies revealed sustained vaginal drug levels of both the drugs exceeding IC₅₀ values with negligible systemic exposure and no mucosal irritation.

Conclusion: These findings demonstrate that enzyme-responsive mucoadhesive bigels represent a safe, effective, and patient-friendly platform for vaginal HIV pre-exposure prophylaxis.

Dr. Sayani Bhattacharyya is a Professor and Head of the Department of Pharmaceutics at Krupanidhi College of Pharmacy, Bengaluru. She is an accomplished academician, researcher, and Ph.D. research guide with extensive experience in pharmaceutical education and research. Her research interests include novel drug delivery systems, nanotechnology-based formulations, and advanced pharmaceutical formulations. She has contributed to several research publications, scholarly activities, and postgraduate research initiatives. She is actively involved in mentoring M.Pharm and Ph.D. scholars, promoting interdisciplinary research, and fostering innovation in pharmaceutical sciences. Her academic contributions reflect a strong commitment to research excellence, quality education, and advancement of pharmaceutical technology.