Liposomes-in-hydrogel delivery system containing resveratrol for the local treatment of vaginal infections

Abstract

Administering drug formulations to the vagina is a challenge since the vagina possesses “self-cleaning” features which allow trapping and rapid removing of foreign particles. Therefore, the residence time of drugs is often too short to offer a sufficient clinical effect. The aim of this project was to develop and optimize a liposomes-in-hydrogel system containing resveratrol for the local treatment of vaginal infections. Resveratrol is a natural occurring compound which could be found in grapes, berries and peanuts. It possesses a number of beneficial effects, and of special relevance is that it has shown to have a potential therapeutic effect against Chlamydia trachomatis. However, there are challenges related to resveratrol which cause difficulties to exploit the favorable clinical effects of it in vaginal delivery. Resveratrol is poorly water soluble and highly sensitive to the exposure of light. To overcome those limitations, resveratrol was encapsulated in liposomes. Moreover, to prolong the resveratrol residence time in the vagina, the resveratrol-liposomes were incorporated (10 %, w/w) in chitosan hydrogel (2.5–3 %, w/w). Chitosan is a polymer which originates from exoskeleton of crustaceans, insects and fungi. The polymer is very attractive considering its known mucoadhesive properties. Liposomes were prepared by the conventional film method. To obtain liposomes in the desired size (200 nm), the liposomes were extruded through polycarbonate membranes. The properties of the liposomes were characterized in respect to entrapment efficiency, zeta potential, size and polydispersity. To optimize the chitosan hydrogels, hydrogels were characterized in regard to texture properties, zeta potential and mucoadhesive properties. The formulation was also tested to confirm the prolonged release profile by performing an in vitro resveratrol release study and an ex vivo penetration study. Resveratrol is also known to have antioxidant properties, and this was confirmed by radical scavenging assay. The radical scavenging activity of resveratrol was compared to the known antioxidants vitamin C and vitamin E.