Development of chitosan-coated liposomes for improved therapy of vaginal infections: clotrimazole as model drug

Abstract

For many drugs the vaginal route of administration is favorable, particularly for local therapy of specific gynecological diseases such as vaginal infections. A large variety of pharmaceutical preparations have been developed for vaginal delivery, nevertheless, the efficiency of currently available dosage forms is often limited by their poor retention time at the vaginal site. Physiological changes and the self-cleansing action of the vaginal tract remain a challenge in formulation development. The aim of this study was development and characterization of mucoadhesive liposomes capable to improve vaginal delivery of clotrimazole. Clotrimazole was incorporated in liposomes by the mechanical dispersion method and the liposomal suspension sonicated to desired vesicle size. Liposomes were characterized for their size, polydipersity and clotrimazole entrapment. Polymer-coating was used to improve the mucoadhesive properties, and chitosan was chosen as a coating material. Chitosan coating (0.1 and 0.6 %, w/v) was performed on liposomes free from unentrapped clotrimazole. In vitro drug release from chitosan-coated liposomes was compared to release from non-coated liposomes and free clotrimazole. Chitosan-coated vesicles were able to prolong the release of entrapped clotrimazole to greater extent than non-coated liposomes. Cow vaginal mucosa was used as model mucosa in both penetration study and mucoadhesion testing and the preliminary data indicate that clotrimazole stays in vaginal tissue, rather than penetrating though the tissue. The experiments confirmed potential of chitosan-coated phospholipid vesicles in treatment of local vaginal diseases.