Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes

Abstract

To increase topical delivery of low-molecular-weight heparin (LMWH), cationic, neutral, and anionic flexible liposomes (cFlexosome, nFlexosome, and aFlexosome) were prepared. The effects of surface charge of Flexosome on physicochemical properties and skin penetration of LMWH were also investigated. Among the different formulations of Flexosome, cFlexosome demonstrated three-times higher entrapment efficiency of LMWH, and better physicochemical stability than nFlexosome and aFlexosome. In vitro skin penetration and in vivo localization into the deeper skin layer of LMWH were significantly greater from cFlexosome compared to other formulations. Changes of skin surface charge after LMWH-cFlexosome application were investigated as a function of time. In the process of skin penetration, the Flexosomes act as drug carrier with the associated LMWH. Overall, macromolecular LMWH could be delivered deeply into the skin by topical application of cFlexosome for the treatment of superficial thrombosis, subcutaneous wounds, bruise, and burns.