International Journal of Nanomedicine (Jul 2023)
Proteinase K/Retinoic Acid-Loaded Cationic Liposomes as Multifunctional Anti-Acne Therapy to Disorganize Biofilm and Regulate Keratinocyte Proliferation
Abstract
Ming-Jun Tsai,1,2 Cheng-Yu Lin,3 Jiří Trousil,4 Calvin T Sung,5 Mei-Hua Lee,3 Jia-You Fang,3,6,7 Shih-Chun Yang8 1School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Jhong Siao Urological Hospital, Kaohsiung, Taiwan; 3Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 4Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic; 5Department of Dermatology, University of California, Irvine, CA, USA; 6Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 7Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 8Department of Microbiology, Soochow University, Taipei, TaiwanCorrespondence: Jia-You Fang, Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan, Email [email protected] Shih-Chun Yang, Department of Microbiology, Soochow University, 70 Linhsi Road, Shihlin, Taipei, 111, Taiwan, Email [email protected]: Simultaneous anti-Cutibacterium acnes and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment.Materials and Methods: This study examined in vitro planktonic and biofilm C. acnes elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating C. acnes in mice were also evaluated.Results: We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm C. acnes colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited C. acnes-stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA—but not free RA—restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing C. acnes colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA.Conclusion: The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.Keywords: liposome, acne, Cutibacterium acnes, proteinase K, retinoic acid, skin delivery
