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Androgenetic alopecia (AGA) is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment, leading to cell apoptosis and eventual loss of hair follicles (HFs). Traditional therapeutic formulations, such as Minoxidil (MXD) tincture, have limitations in reshaping the perifollicular microenvironment and exhibit limited effectiveness. Here, we report a multi-synergistic therapeutic platform for high-performance hair regeneration therapy. The platform combines microneedle (MN) patches loaded with MXD-encapsulated nanostructured lipid carriers (MXD-NLC-MNs) and cold atmospheric plasma (CAP). The MNs’ mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells, promoting cell proliferation. Furthermore, in collaboration with MXD, the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor, leading to neoangiogenesis. Meanwhile, the transient microchannels in the skin created by MNs facilitate the transdermal delivery of CAP-generated nitric oxide (NO) to the sites of HF lesions, whereby the synergistic interaction between MXD and NO boosts perifollicular vasodilation. Consequently, the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine models. This multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth.


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Remodel the perifollicular microenvironment via Minoxidil-loaded microneedle patch and cold atmospheric plasma for treating androgenetic alopecia

Show Author's information Hao Chen1Xianzhe Tang1Yueye Huang2,3Chen Chen1( )Yuheng Yang1Chaojie Hao1Wenqi Xie1Tingjing Huang1Xiaofeng Cheng1Qingnan Xu2Shicong Huang3Zhi Ye1,4Xucong Lin5Zhaowei Chen1,5( )Zhitong Chen2,3,6( )
MOE Key Laboratory for Analytical Science of Food Safety and Biology, and New Cornerstone Science Laboratory, College of Chemistry, Fuzhou University, Fuzhou 350108, China
Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Advanced Therapeutic Center, National Innovation Center for Advanced Medical Devices, Shenzhen 518000, China
Department of Chemistry, University College London, London WC1H 0AJ, UK
Engineering Technology Research Center on Reagent and Instrument for Rapid Detection of Product Quality and Food Safety in Fujian Province, College of Chemistry, Fuzhou University, Fuzhou 350108, China
Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, Shenzhen 518055, China

Abstract

Androgenetic alopecia (AGA) is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment, leading to cell apoptosis and eventual loss of hair follicles (HFs). Traditional therapeutic formulations, such as Minoxidil (MXD) tincture, have limitations in reshaping the perifollicular microenvironment and exhibit limited effectiveness. Here, we report a multi-synergistic therapeutic platform for high-performance hair regeneration therapy. The platform combines microneedle (MN) patches loaded with MXD-encapsulated nanostructured lipid carriers (MXD-NLC-MNs) and cold atmospheric plasma (CAP). The MNs’ mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells, promoting cell proliferation. Furthermore, in collaboration with MXD, the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor, leading to neoangiogenesis. Meanwhile, the transient microchannels in the skin created by MNs facilitate the transdermal delivery of CAP-generated nitric oxide (NO) to the sites of HF lesions, whereby the synergistic interaction between MXD and NO boosts perifollicular vasodilation. Consequently, the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine models. This multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth.

Keywords: drug delivery, nanomedicine, microneedle, androgenetic alopecia, cold atmospheric plasma

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Publication history
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Acknowledgements

Publication history

Received: 21 January 2024
Revised: 06 March 2024
Accepted: 11 March 2024
Published: 04 April 2024

Copyright

© Tsinghua University Press 2024

Acknowledgements

Acknowledgements

This work was supported by the National Key Research and Development Program of China (Nos. 2022YFE0126000 (Zhitong Chen), and 2020YFA0210800 (Zhaowei Chen)), the National Natural Science Foundation of China (Nos. 22277011 (Zhaowei Chen), and 22107019 (Zhaowei Chen)), the Major Project of Science and Technology of Fujian Province (No. 2020HZ06006 (Zhaowei Chen)), and the Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515011129 (Zhitong Chen)).

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