Formulation matters: Assessment of the correlation between mucoadhesiveness and type of chitosan formulation for vaginal application

Abstract

Localized vaginal drug delivery can offer safer and more effective treatment options for various conditions, also for pregnant women. However, inadequate retention of formulation in the vaginal cavity hinders efficient treatment. Mucoadhesive drug delivery systems using mucoadhesive polymers may be a promising solution. In this work, the biopolymer chitosan was chosen for its well documented mucoadhesive properties, favorable biopharmaceutical profile, and low toxicity. However, its mucoadhesive abilities may depend on how chitosan is formulated. This study therefore focused on two distinct chitosan formulations, chitosan-coated liposomes and liposomes-in-chitosan hydrogel, to compare mucoadhesiveness across formulations. Additionally, two chitosan molecular weights (LMW and MMW) and four concentrations (0.1 %, 0.3 %, 0.6 % and 1.0 %) were examined, whilst considering site-specific factors like pH, biological fluids, and temperature. The formulations were characterized, and their mucoadhesive behavior evaluated by monitoring changes in viscosity and zeta potential upon mixing with mucin. Liposomes averaged 135 nm in size with a zeta potential of −2.78 mV, where the charge increased with chitosan coating or incorporation into chitosan hydrogel. Both chitosan-coated liposomes and liposomes-in-hydrogel exhibited rheological properties suitable for vaginal application. Mucoadhesion indeed varied based on the formulation, chitosan concentration, molecular weight, pH, and temperature. Notably, liposomes-in-hydrogel formulations demonstrated superior mucoadhesive potential. These findings emphasize the importance of formulation design and environmental factors in optimizing mucoadhesion.