目的 研究钙黄绿素神经酰胺脂质体(calcein-loaded cerasomes, CA-CS)的体外皮内递送效果,并推测其皮内递送的主要机制。方法 采用薄膜水化-冻融法制备CA-CS和钙黄绿素传统脂质体(calcein-loaded conventional liposomes, CA-CL),并对其理化性质和体外释放行为进行表征;采用改良的Franz透皮扩散仪和大鼠皮肤进行体外皮内递送实验;使用荧光显微镜观察药物在皮肤中的分布。结果 CA-CS和 CA-CL的粒径均在200 nm左右,且分散均匀(PDI＜0.3),体外释放结果显示,CA-CS和CA-CL均具有良好的缓释作用;体外皮内递送实验和荧光显微镜结果显示,8 h内CA-CS的皮内滞留量显著高于CA-CL和钙黄绿素溶液,分别约是它们的2倍和1.6倍,且神经酰胺脂质体能将钙黄绿素递送至更深的皮肤层。结论 神经酰胺脂质体与皮肤角质层具有较强的相互作用,能显著提高水溶性药物的皮内递送效果,实现皮肤靶向给药的目的, 为皮肤局部给药提供了一种有效的药物载体。
Abstract
OBJECTIVE To investigate the in vitro intradermal delivery effect of calcein-loaded cerasomes (CA-CS) and reveal its main mechanism of skin delivery. METHODS CA-CS and calcein-loaded conventional liposomes (CA-CL) were prepared by a thin layer and freeze-thaw method and their physicochemical properties and in vitro release profiles were characterized. The in vitro dermal delivery experiments of calcein-loaded cerasomes through rat skin were performed using Franz′s cells. The drug distribution in skin was observed using fluorescence microscope. RESULTS CA-CS and CA-CL were both about 200 nm and uniformly dispersed(PDI＜0.3). The in vitro release test showed sustained release both from CA-CS and CA-CL. The in vitro cutaneous delivery experiment and fluorescence microscopy results showed that the skin retention of calcein from CA-CS was significantly higher than that of calcein from CA-CL (about 2 times) and calcein solution (about 1.6 times) within 8 h, and cerasomes can delivery calcein into the deeper layer of the skin. CONCLUSION Cerasomes have a strong interaction with the skin stratum corneum, which can significantly improve the intradermal delivery effect of water-soluble drugs and achieve the purpose of skin-targeted drug delivery.
关键词
神经酰胺脂质体 /
钙黄绿素 /
皮内递送 /
皮肤靶向 /
局部给药
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Key words
cerasome /
calcein /
dermal delivery /
skin-targeted /
topical delivery
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中图分类号：
R944
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参考文献
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