Effects of surface charge and flexibility of liposomes on dermal drug delivery

Dermal drug delivery is noninvasive and improves patient's quality of life. However, the stratum corneum and tight junctions in the granular layer are barriers that impede the delivery of hydrophilic macromolecules. For use in the treatment of allergic diseases, the drug must be delivered to deep sites within the skin, where immune-competent cells are located. Several liposome preparations have been reported to improve dermal drug delivery. However, there are few systematic reports on intradermal penetration of liposomes that focused on liposomal characteristics. In the present study, we aimed to investigate the characteristics of liposomes, which facilitates effective intradermal penetration, by focusing on their surface charge and structural flexibility. Liposomes with various surface charges and structures were prepared and their physical properties, flexibility, intradermal penetration, cytotoxicity, skin irritation, and intracellular uptake ability were evaluated. Three types of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol-based cationic, neutral, and anionic liposomes and another anionic 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS) liposome were tested. Cellular uptake and intradermal penetration of liposomes were affected by surface charge and flexibility. DOPE/CHEMS liposome showed the most effective intradermal penetration and lowest skin irritation induction. In conclusion, the combination of negative surface charge and flexible structure is required for effective dermal drug delivery using liposomes.