Topical vaginal therapy: Development of a liposomal hydrogel delivery system for epicatechin

Abstract

Vaginal infections are common in women of all ages and proper treatment is essential. The vaginal route of administration can be considered as favourable for the local therapy of vaginal infections. There are several vaginal dosage forms currently available; however, all suffer from limitations such as leakage and limited residence time at the site of action resulting in reduced therapeutic effect. Epicatechin (EC) is thought to be a potential substance in the both prevention and treatment of vaginal infections due to its antioxidative and anti-inflammatory effects, potentially also antimicrobial. However, the physiochemical properties of EC limit its use, and EC is a good candidate to exploit the beneficial effects of delivery system on improved therapeutic action. A delivery system with suitable viscosity and good mucoadhesive properties was the focus of this project; liposomal hydrogel comprising liposomes containing EC and chitosan hydrogel as a vehicle was developed. Phosphatidylcholine liposomes containing EC were made by the thin film method followed by extrusion to desired size of 200 nm. Liposomal EC were characterized for vesicle size, polydispersity and EC entrapment efficiency. We prepared liposomes of desired vesicle size (around 200 nm) with rather high EC load (over 80 % entrapment efficacy). Liposomal EC suspensions were further incorporated in a chitosan hydrogel vehicle, and the texture properties of the hydrogel investigated to optimize the formulation. The hydrogels were found to have satisfactory cohesiveness, adhesiveness and hardness as well as satisfactory mucoadhesive properties, however, further investigation and optimization of the method is needed. Liposomal EC and liposomal EC hydrogel were found to provide prolonged EC release. High accumulation of EC at the ex vivo vaginal tissue confirmed that liposomal EC hydrogels could assure localized vaginal delivery.

Key words: Liposomes, chitosan hydrogel, epicatechin, mucoadhesion, vaginal delivery