中国药科大学学报2025，Vol.56Issue(6)：719-728,10.DOI:10.11665/j.issn.1000-5048.2025051201
透明质酸-磷脂胶束包载雷公藤甲素皮肤给药治疗银屑病的研究
Research on the transdermal delivery of triptolide encapsulated in hyaluronic acid-phospholipid micelles for the treatment of psoriasis
摘要
Abstract
Psoriasis,a chronic,immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes,is difficult to cure and prone to relapse,often leading to systemic damage.Triptolide(TPL)can modulate cutaneous immune responses and inflammation,yet its therapeutic window is narrow with significant toxicity.To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity,a TPL/hyaluronic acid/phospholipid polymeric micelle(TPL/HA-DOPE)was constructed via HA's targeting of the CD44 receptor on skin cells.The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of(130.4±1.23)nm,drug loading capacity of(19.74±0.084)%,and encapsulation efficiency of(85.53±1.34)%.Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention.In a murine model of psoriasis,the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d)showed the most significant improvement in erythema,scaling,and epidermal thickening.Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness,epidermal hyperplasia,and inflammatory cell infiltration.Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α.The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.关键词
银屑病/雷公藤甲素/透明质酸-磷脂聚合物/聚合物胶束/皮肤储留Key words
psoriasis/triptolide/hyaluronic acid-phospholipid/polymeric micelles/skin retention分类
医药卫生引用本文复制引用
王小莉,刘湘怡,宁晓慧,张振海,王玉玲,鲍玉,吕慧侠,朱沛维..透明质酸-磷脂胶束包载雷公藤甲素皮肤给药治疗银屑病的研究[J].中国药科大学学报,2025,56(6):719-728,10.基金项目
中国药科大学皮肤有组织科研药物研发赛道-化妆品赛道(No.3342400034) This study was supported by the Organized Scientific Research and Development Project(the Cosmetic Tract)of China Pharmaceutical University(No.3342400034) （No.3342400034）
