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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.

Bacterial biofilms (BBFs) are frequently formed on medical devices such as catheters. They act as barriers and reduce the concentration of antimicrobial agents that reach the bacteria located on the inside of BBFs. Hence, BBF-forming bacteria cause intractable and chronic infections. At present, there is no effective treatment for BBF-associated infections. We aimed to develop the liposomes that can efficiently deliver antimicrobial agents to bacteria located inside BBFs. First, we designed liposomes with different surface properties using ionic lipids, cholesterol, and PEG-modified lipids. The minimum inhibitory concentration (MIC), permeability, retention, and anti-BBF effect of liposomes against Pseudomonas aeruginosaPAO-1 were examined. The MIC test showed that no antimicrobial activity was found in the liposomes tested. Cationic liposomes had high anti-BBF effect and retention on BBF, whereas anionic liposomes showed high permeability to BBF. In addition, PEG modification increased the anti-BBF effect but reduced the retention of liposomes on BBF. In conclusion, controlling surface charge and PEG modification contribute to the effectiveness of liposomes against BBFs. Liposomes for which surface properties can be easily controlled will become an effective tool for the treatment of BBF-associated infections.