Citation: Jushan Gao, Shanbo Ma, Xinxin Zhao, Jinpeng Wen, Datao Hu, Xiaoye Zhao, Xiaopeng Shi, Ke Wang. Dual-labeled visual tracer system for topical drug delivery by nanoparticle-triggered P-glycoprotein silencing[J]. Chinese Chemical Letters, ;2021, 32(12): 3954-3961. doi: 10.1016/j.cclet.2021.06.040 shu

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

Jushan Gao ^{a, 1} ,
Shanbo Ma ^{b, 1} ,
Xinxin Zhao ^a ,
Jinpeng Wen ^a ,
Datao Hu ^a ,
Xiaoye Zhao ^a ,
Xiaopeng Shi ^{b, *,} ,
Ke Wang ^{a, *,}

a.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
b.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China

shixiaopeng775471@163.com

perpetual1003@mail.xjtu.edu.cn

Received Date: 1 April 2021
Revised Date: 10 June 2021
Accepted Date: 14 June 2021
Available Online: 24 June 2021

Figures(5)

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 HaCaT cells, including changes in cell membrane potential, intracellular Ca²⁺ concentration, and Ca²⁺-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 Ca²⁺ concentration, and decreasing Ca²⁺-ATPase activity, our results indicate that the dual-labeled 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.
- Transdermal delivery,
- Nanoparticle,
- Stratum corneum,
- Dermis,
- Transdermal enhancer
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