Dual-labeled visual tracer system for topical drug delivery by nanoparticle-triggered P-glycoprotein silencing  

作　　者：Jushan Gao Shanbo Ma Xinxin Zhao Jinpeng Wen Datao Hu Xiaoye Zhao Xiaopeng Shi Ke Wang 

机构地区：[1]School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China [2]Department of Pharmacy,Xijing Hospital,Fourth Military Medical University,Xi'an 710032,China

出　　处：《Chinese Chemical Letters》2021年第12期3954-3961,共8页中国化学快报（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (No. 81773686);the Natural Science Foundation of Shaanxi Province, China (Nos. 2021SF-108, 2021SF-308)。

摘　　要：Using nanoparticle-based drug delivery systems as enhancers is a robust strategy for transdermal delivery;however, the mechanisms by which these systems promote transdermal penetration are still unclear.Here, we fabricated a dual-labeled nano drug delivery system that allows discrete visualization of both the drug and the nanoparticle carrier. To comprehensively examine its potential mechanism, we investigated its effects on human epidermal keratinocyte Ha Ca T cells, including changes in cell membrane potential, intracellular Ca;concentration, and Ca;-ATPase activity. P-glycoprotein(P-gp) expression in nanoparticle-treated human dermal microvascular endothelial cells was detected by western blotting and immunofluorescence. Furthermore, the transdermal absorption and biodistribution of the dual-labeled nanoparticles were deeply investigated by skin permeability study in vitro and in vivo using fluorescence microscopy and in vivo imaging, respectively. In addition to reducing membrane potential, increasing the intracellular Ca;concentration, and decreasing Ca;-ATPase activity, our results indicate that the duallabeled nanoparticles can downregulate P-gp to promote transdermal absorption. Fluorescence and in vivo imaging visually demonstrated that the nanoparticle delivery system penetrated into the dermis through the stratum corneum. All these results indicate that this dual-labeled nano delivery system provides a new method for future in-depth visual explorations of transdermal drug delivery mechanisms.

关 键 词：Transdermal delivery NANOPARTICLE Stratum corneum DERMIS Transdermal enhancer 

分 类 号：TQ460.4[化学工程—制药化工]