He Weiyi, Zhang Chi, Lai Huijung, Wu Guopeng, Xiong Ming, Peng Hui, Chen Ming, Wang Ke-Jian
Department of Marine Biological Science & Technology, College of Ocean & Earth Sciences, Xiamen University, Xiamen, 361102, China.
State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, Xiamen University, Xiamen, 361102, China.
Drug Deliv Transl Res. 2025 Apr;15(4):1411-1423. doi: 10.1007/s13346-024-01687-7. Epub 2024 Aug 6.
We demonstrated for the first time that a marine-derived antimicrobial peptide (AMP), Sph, exhibit high antimicrobial activity against P. acnes with a minimum bactericidal concentration (MBC) value of 7 μM. Meanwhile, Sph has no significant cytotoxicity to human keratinocytes (HKs) at its high concentration (33.5 μM). The topical application of sponge Haliclona sp. spicules (SHS) dramatically enhanced the skin penetration of Sph up to 40.9 ± 5.9% (p < 0.01), which was 6.1 ± 0.9-fold higher than that of Sph alone. Further, SHS resulted in the accumulation of most Sph in viable epidermis and dermis. Further, the combined use of Sph and SHS resulted in a cure rate of 100% for rabbit ear acne treatment in vivo for two weeks, while the one induced by other groups was 40%, 0% and 0% for SHS alone, Sph alone and control group, respectively. The strategy of combined using AMP and SHS can also be applied in a rational designed topical delivery system for the management of other deep infection of the skin. The effectiveness of SHS by itself on the treatment of acne was also demonstrated by clinical trials. After 14 days of treatment by 1% SHS gel. The number of skin lesions decreased by 51.4%.
我们首次证明,一种海洋来源的抗菌肽(AMP)——Sph,对痤疮丙酸杆菌具有高抗菌活性,其最低杀菌浓度(MBC)值为7 μM。同时,Sph在高浓度(33.5 μM)时对人角质形成细胞(HKs)无明显细胞毒性。海绵Haliclona sp.骨针(SHS)的局部应用显著增强了Sph的皮肤渗透,高达40.9±5.9%(p<0.01),比单独使用Sph高6.1±0.9倍。此外,SHS导致大部分Sph在活表皮和真皮中积累。此外,Sph和SHS联合使用在体内治疗兔耳痤疮两周的治愈率为100%,而单独使用SHS、单独使用Sph和对照组的治愈率分别为40%、0%和0%。联合使用AMP和SHS的策略也可应用于合理设计的局部给药系统,用于治疗其他皮肤深部感染。临床试验也证明了SHS自身治疗痤疮的有效性。用1% SHS凝胶治疗14天后,皮肤损伤数量减少了51.4%。