Enhancing transdermal delivery of chrysomycin A for the treatment of cutaneous melanoma and MRSA infections using Skin-Penetrating Peptide-Functionalized deformable liposomes

Yue Cai; Xinrui Zhang; Wentao Hu; Fuhang Song; Hong Wang; Huawei Zhang; Xuanrong Sun

doi:10.1016/j.ijpharm.2024.125130

Enhancing transdermal delivery of chrysomycin A for the treatment of cutaneous melanoma and MRSA infections using Skin-Penetrating Peptide-Functionalized deformable liposomes

Int J Pharm. 2024 Dec 24:670:125130. doi: 10.1016/j.ijpharm.2024.125130. Online ahead of print.

Authors

Yue Cai¹, Xinrui Zhang¹, Wentao Hu¹, Fuhang Song², Hong Wang³, Huawei Zhang⁴, Xuanrong Sun⁵

Affiliations

¹ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, 310014 Hangzhou, China.
² Key Laboratory of Geriatric Nutrition and Health, Ministry of Education of China, School of Light Industry Science and Engineering, Beijing Technology and Business University, 100048 Beijing, China.
³ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, 310014 Hangzhou, China; Zhejiang Key Laboratory of Green, Low-carbon and Efficient Development of Marine Fishery Resources, Hangzhou 310014, China.
⁴ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, 310014 Hangzhou, China; Zhejiang Key Laboratory of Green, Low-carbon and Efficient Development of Marine Fishery Resources, Hangzhou 310014, China. Electronic address: [email protected].
⁵ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, 310014 Hangzhou, China; Zhejiang Key Laboratory of Green, Low-carbon and Efficient Development of Marine Fishery Resources, Hangzhou 310014, China. Electronic address: [email protected].

PMID: 39722374
DOI: 10.1016/j.ijpharm.2024.125130

Abstract

Transdermal drug delivery represents a promising avenue for the treatment of dermatologic diseases, such as cutaneous melanoma and skin infections. This study involves the development of a novel therapeutic strategy that employs a skin-penetrating peptide SPACE-modified flexible liposomal chrysomycin A (CA@SPACE-LP) with a particle size of 111.5 nm. In vitro transdermal experiments demonstrated that CA@SPACE-LP was effective in enhancing the ability of the drug to penetrate the stratum corneum and enter deep into the skin tissue, increasing the intradermal drug concentration up to threefold compared to free CA. Furthermore, CA@SPACE-LP was observed to maintain the biological activity of CA against planktonic Methicillin-resistant Staphylococcus aureus (MRSA) and melanoma cells. In vivo studies demonstrated that the topical administration of CA@SPACE-LP was efficacious in controlling the progression of cutaneous melanoma, with a tumor suppression rate of approximately 60 %, which was more pronounced than that observed with intravenous Taxol. Furthermore, CA@SPACE-LP demonstrated efficacy in the management of intradermal MRSA infections, with a significantly reduced area of ulceration in the treated mice (0.25 cm²) compared to the positive control drug (Mupirocin Ointment). These results suggest that the topical delivery system developed in this study has the potential to be used for the simultaneous treatment of skin cancer and invasive MRSA infection.

Keywords: Chrysomycin A; Flexible liposome; MRSA; Melanoma; Skin penetration.