摘要
银屑病是一种由免疫介导的慢性、炎症性疾病,难根治,易复发,并可导致全身损害;角质形成细胞过度增殖是银屑病的主要特征。雷公藤甲素(triptolide,TPL)可以调控皮肤的免疫和炎症反应,抑制角质形成细胞过度增殖,然而其存在治疗窗狭窄、副作用大的问题。利用透明质酸(HA)对皮肤细胞上CD44受体的靶向能力,构建了TPL/透明质酸/磷脂聚合物胶束(TPL/HA-DOPE),以提高TPL的皮肤渗透和储留,降低其全身吸收,提高其治疗银屑病的效果。制备而成的TPL/HADOPE为均匀的球形结构,粒径为(130.4±1.23)nm,载药量为(19.74±0.084)%,包封率为(85.53±1.34)%。体内外实验证明TPL/HA-DOPE不仅可以提高Hacat细胞对其的摄取,还具有良好的皮肤储留效果。TPL/HA-DOPE[50μg/(kg•d)])组在银屑病小鼠模型上的结果表明,其可以显著改善银屑病皮肤的红斑、鳞屑和增厚程度;并可以极大地降低角质层厚度,减少表皮增生和炎症细胞浸润现象;Ki67染色检测证明其抗炎机制可能是通过减少Ki67阳性细胞数量和降低炎症因子IL-6和TNF-α水平而实现。以上结果证明HA-DOPE作为给药载体治疗银屑病类皮肤疾病具有较高的科学研究价值和良好的临床应用前景。
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 50μg/(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.
作者
王小莉
刘湘怡
宁晓慧
张振海
王玉玲
鲍玉
吕慧侠
朱沛维
WANG Xiaoli;LIU Xiangyi;NING Xiaohui;ZHANG Zhenhai;WANG Yuling;BAO Yu;LYU Huixia;ZHU Peiwei(Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028;Academy of Traditional Chinese Medicine,Nanjing 210028;School of Pharmacy,China Pharmaceutical University,Nanjing 210009;Fuqirui Pharmaceutical Research and Development Co.,Ltd.,Beijing 100020;School of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074;Huaxi Biotechnology Co.,Ltd.,Jinan 250101,China)
出处
《中国药科大学学报》
北大核心
2025年第6期719-728,共10页
Journal of China Pharmaceutical University
基金
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)。
