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Research Article

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

Hao Chen1, Xianzhe Tang1, Yueye Huang2,3, Chen Chen1( ), Yuheng Yang1, Chaojie Hao1, Wenqi Xie1, Tingjing Huang1, Xiaofeng Cheng1, Qingnan Xu2, Shicong Huang3, Zhi Ye1,4, Xucong Lin5, Zhaowei 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
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Graphical Abstract

A multi-synergistic therapeutic strategy that combines nano-formulated minoxidil, microneedle patch and cold atmospheric plasma is developed for high-performance androgenetic alopecia treatment. By harnessing the synergistic effects of these therapeutics, this strategy efficiently remodels the perifollicular microenvironment and promotes hair regeneration.

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

nanomedicineandrogenetic alopeciamicroneedlecold atmospheric plasmadrug delivery

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References

[1]

Yap, C. X.; Sidorenko, J.; Wu, Y.; Kemper, K. E.; Yang, J.; Wray, N. R.; Robinson, M. R.; Visscher, P. M. Dissection of genetic variation and evidence for pleiotropy in male pattern baldness. Nat. Commun. 2018, 9, 5407.
Crossref Google Scholar
[2]

Heilmann-Heimbach, S.; Herold, C.; Hochfeld, L. M.; Hillmer, A. M.; Nyholt, D. R.; Hecker, J.; Javed, A.; Chew, E. G. Y.; Pechlivanis, S.; Drichel, D. et al. Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness. Nat. Commun. 2017, 8, 14694.
Crossref Google Scholar
[3]

Yang, G.; Chen, G. J.; Gu, Z. Transdermal drug delivery for hair regrowth. Mol. Pharmaceutics 2021, 18, 483–490.
Crossref Google Scholar
[4]

Yang, G.; Chen, Q.; Wen, D.; Chen, Z. W.; Wang, J. Q.; Chen, G. J.; Wang, Z. J.; Zhang, X. D.; Zhang, Y. Q.; Hu, Q. Y. et al. A therapeutic microneedle patch made from hair-derived keratin for promoting hair regrowth. ACS Nano 2019, 13, 4354–4360.
Crossref Google Scholar
[5]

Yuan, A. R.; Gu, Y. T.; Bian, Q.; Wang, R. X.; Xu, Y. H.; Ma, X. L.; Zhou, Y. J.; Gao, J. Q. Conditioned media-integrated microneedles for hair regeneration through perifollicular angiogenesis. J. Controlled Release 2022, 350, 204–214.
Crossref Google Scholar
[6]

Gupta, A. K.; Talukder, M.; Venkataraman, M.; Bamimore, M. A. Minoxidil: A comprehensive review. J. Dermatol. Treat. 2022, 33, 1896–1906.
Crossref Google Scholar
[7]

Messenger, A. G.; Rundegren, J. Minoxidil: Mechanisms of action on hair growth. Br. J. Dermatol. 2004, 150, 186–194.
Crossref Google Scholar
[8]

Suchonwanit, P.; Thammarucha, S.; Leerunyakul, K. Minoxidil and its use in hair disorders: A review. Drug Des. Dev. Ther. 2019, 13, 2777–2786.
Crossref Google Scholar
[9]

Lu, Z. Y.; Du, S.; Li, J. X.; Zhang, M.; Nie, H. L.; Zhou, X. J.; Li, F. L.; Wei, X. W.; Wang, J. Q.; Liu, F. Y. et al. Langmuir-Blodgett-mediated formation of antibacterial microneedles for long-term transdermal drug delivery. Adv. Mater. 2023, 35, 2303388.
Crossref Google Scholar
[10]

Zhou, X. W.; Luo, Z. M.; Baidya, A.; Kim, H. J.; Wang, C. R.; Jiang, X.; Qu, M. Y.; Zhu, J. X.; Ren, L.; Vajhadin, F. et al. Biodegradable β-cyclodextrin conjugated gelatin methacryloyl microneedle for delivery of water-insoluble drug. Adv. Healthcare Mater. 2020, 9, 2000527.
Crossref Google Scholar
[11]

Qu, M. Y.; Kim, H. J.; Zhou, X. W.; Wang, C. R.; Jiang, X.; Zhu, J. X.; Xue, Y. M.; Tebon, P.; Sarabi, S. A.; Ahadian, S. et al. Biodegradable microneedle patch for transdermal gene delivery. Nanoscale 2020, 12, 16724–16729.
Crossref Google Scholar
[12]

Larrañeta, E.; Lutton, R. E. M.; Woolfson, A. D.; Donnelly, R. F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng.: R: Rep. 2016, 104, 1–32.
Crossref Google Scholar
[13]

Caffarel-Salvador, E.; Kim, S.; Soares, V.; Tian, R. Y.; Stern, S. R.; Minahan, D.; Yona, R.; Lu, X. Y.; Zakaria, F. R.; Collins, J. et al. A microneedle platform for buccal macromolecule delivery. Sci. Adv. 2021, 7, eabe2620.
Crossref Google Scholar
[14]

Chen, Z. W.; Li, H. J.; Bian, Y. J.; Wang, Z. J.; Chen, G. J.; Zhang, X. D.; Miao, Y. M.; Wen, D.; Wang, J. Q.; Wan, G. et al. Bioorthogonal catalytic patch. Nat. Nanotechnol. 2021, 16, 933–941.
Crossref Google Scholar
[15]

Chen, Q.; Xiao, Z. S.; Wang, C.; Chen, G. J.; Zhang, Y. Q.; Zhang, X. D.; Han, X.; Wang, J. Q.; Ye, X.; Prausnitz, M. R. et al. Microneedle patches loaded with nanovesicles for glucose transporter-mediated insulin delivery. ACS Nano 2022, 16, 18223–18231.
Crossref Google Scholar
[16]

Yu, J. C.; Zhang, Y. Q.; Ye, Y. Q.; DiSanto, R.; Sun, W. J.; Ranson, D.; Ligler, F. S.; Buse, J. B.; Gu, Z. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc. Natl. Acad. Sci. USA 2015, 112, 8260–8265.
Crossref Google Scholar
[17]

Chang, H.; Chew, S. W. T.; Zheng, M. J.; Lio, D. C. S.; Wiraja, C.; Mei, Y.; Ning, X. Y.; Cui, M. Y.; Than, A.; Shi, P. et al. Cryomicroneedles for transdermal cell delivery. Nat. Biomed. Eng. 2021, 5, 1008–1018.
Crossref Google Scholar
[18]

Li, W.; Terry, R. N.; Tang, J.; Feng, M. R.; Schwendeman, S. P.; Prausnitz, M. R. Rapidly separable microneedle patch for the sustained release of a contraceptive. Nat. Biomed. Eng. 2019, 3, 220–229.
Crossref Google Scholar
[19]

Chen, Z. T.; Chen, G. J.; Obenchain, R.; Zhang, R.; Bai, F.; Fang, T. X.; Wang, H. W.; Lu, Y. J.; Wirz, R. E.; Gu, Z. Cold atmospheric plasma delivery for biomedical applications. Mater. Today 2022, 54, 153–188.
Crossref Google Scholar
[20]

Bourke, P.; Ziuzina, D.; Boehm, D.; Cullen, P. J.; Keener, K. The potential of cold plasma for safe and sustainable food production. Trends Biotechnol. 2018, 36, 615–626.
Crossref Google Scholar
[21]

Chen, Z. T.; Garcia, G, Jr.; Arumugaswami, V.; Wirz, R. E. Cold atmospheric plasma for SARS-CoV-2 inactivation. Phys. Fluids 2020, 32, 111702.
Crossref Google Scholar
[22]

Chen, G. J.; Chen, Z. T.; Wang, Z. J.; Obenchain, R.; Wen, D.; Li, H. J.; Wirz, R. E.; Gu, Z. Portable air-fed cold atmospheric plasma device for postsurgical cancer treatment. Sci. Adv. 2021, 7, eabg5686.
Crossref Google Scholar
[23]

Chen, G. J.; Chen, Z. T.; Wen, D.; Wang, Z. J.; Li, H. J.; Zeng, Y.; Dotti, G.; Wirz, R. E.; Gu, Z. Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy. Proc. Natl. Acad. Sci. USA 2020, 117, 3687–3692.
Crossref Google Scholar
[24]

Esposito, E.; Drechsler, M.; Cortesi, R.; Nastruzzi, C. Encapsulation of cannabinoid drugs in nanostructured lipid carriers. Eur. J. Pharm. Biopharm. 2016, 102, 87–91.
Crossref Google Scholar
[25]

Chen, Z. W.; Liu, Z.; Li, Z. H.; Ju, E. G.; Gao, N.; Zhou, L.; Ren, J. S.; Qu, X. G. Upconversion nanoprobes for efficiently in vitro imaging reactive oxygen species and in vivo diagnosing rheumatoid arthritis. Biomaterials 2015, 39, 15–22.
Crossref Google Scholar
[26]

Chen, Z. W.; Li, Z. H.; Wang, J. S.; Ju, E. G.; Zhou, L.; Ren, J. S.; Qu, X. G. A multi-synergistic platform for sequential irradiation-activated high-performance apoptotic cancer therapy. Adv. Funct. Mater. 2014, 24, 522–529.
Crossref Google Scholar
[27]

Du, H. Y.; Liu, P.; Zhu, J. J.; Lan, J. J.; Li, Y.; Zhang, L. B.; Zhu, J. T.; Tao, J. Hyaluronic acid-based dissolving microneedle patch loaded with methotrexate for improved treatment of psoriasis. ACS Appl. Mater. Interfaces 2019, 11, 43588–43598.
Crossref Google Scholar
[28]

Wang, C.; Ye, Y. Q.; Hochu, G. M.; Sadeghifar, H.; Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PD1 antibody. Nano Lett. 2016, 16, 2334–2340.
Crossref Google Scholar
[29]

Yang, C. W.; Sheng, T.; Hou, W. H.; Zhang, J.; Cheng, L.; Wang, H.; Liu, W.; Wang, S. Q.; Yu, X. M.; Zhang, Y. Q. et al. Glucose-responsive microneedle patch for closed-loop dual-hormone delivery in mice and pigs. Sci. Adv. 2022, 8, eadd3197.
Crossref Google Scholar
[30]

Sullivan, S. P.; Koutsonanos, D. G.; del Pilar Martin, M.; Lee, J. W.; Zarnitsyn, V.; Choi, S. O.; Murthy, N.; Compans, R. W.; Skountzou, I.; Prausnitz, M. R. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med. 2010, 16, 915–920.
Crossref Google Scholar
[31]

Aljuffali, I. A.; Pan, T. L.; Sung, C. T.; Chang, S. H.; Fang, J. Y. Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells. Nanomedicine: Nanotechnol. Biol. Med. 2015, 11, 1321–1330.
Crossref Google Scholar
[32]

Lin, Y. K.; Al-Suwayeh, S. A.; Leu, Y. L.; Shen, F. M.; Fang, J. Y. Squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata. Pharm. Res. 2013, 30, 435–446.
Crossref Google Scholar
[33]

Kapaldo, J.; Han, X.; Ptasinska, S. Shielding-gas-controlled atmospheric pressure plasma jets: Optical emission, reactive oxygen species, and the effect on cancer cells. Plasma Processes Polym. 2019, 16, 1800169.
Crossref Google Scholar
[34]

Shekhter, A. B.; Serezhenkov, V. A.; Rudenko, T. G.; Pekshev, A. V.; Vanin, A. F. Beneficial effect of gaseous nitric oxide on the healing of skin wounds. Nitric Oxide 2005, 12, 210–219.
Crossref Google Scholar
[35]

Yano, K.; Brown, L. F.; Detmar, M. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J. Clin. Invest. 2001, 107, 409–417.
Crossref Google Scholar
[36]

Przybylski, M. A review of the current research on the role of bFGF and VEGF in angiogenesis. J. Wound Care 2009, 18, 516–519.
Crossref Google Scholar
[37]

Zhou, Y. J.; Jia, L.; Zhou, D.; Chen, G.; Fu, Q.; Li, N. Advances in microneedles research based on promoting hair regrowth. J. Controlled Release 2023, 353, 965–974.
Crossref Google Scholar
[38]

Fakhraei Lahiji, S.; Seo, S. H.; Kim, S.; Dangol, M.; Shim, J.; Li, C. G.; Ma, Y. H.; Lee, C.; Kang, G.; Yang, H. et al. Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth. Biomaterials 2018, 167, 69–79.
Crossref Google Scholar
[39]

Yum, S.; Jeong, S.; Kim, D.; Lee, S.; Kim, W.; Yoo, J. W.; Kim, J. A.; Kwon, O. S.; Kim, D. D.; Min, D. S. et al. Minoxidil induction of VEGF is mediated by inhibition of HIF-prolyl hydroxylase. Int. J. Mol. Sci. 2018, 19, 53.
Crossref Google Scholar
[40]

Marubayashi, A.; Nakaya, Y.; Fukui, K.; Li, M.; Arase, S. Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: Possible involvement of sulfonylurea receptor 2B as a target of minoxidil. J. Invest. Dermatol. 2001, 117, 1594–1600.
Crossref Google Scholar
[41]

Zhang, Z. W. B.; Li, W. B.; Liu, Y.; Yang, Z. G.; Ma, L. L.; Zhuang, H.; Wang, E. D.; Wu, C. T.; Huan, Z. G.; Guo, F. et al. Design of a biofluid-absorbing bioactive sandwich-structured Zn-Si bioceramic composite wound dressing for hair follicle regeneration and skin burn wound healing. Bioact. Mater. 2021, 6, 1910–1920.
Crossref Google Scholar
[42]

Ma, W. J.; Zhang, X. X.; Liu, Y. X.; Fan, L.; Gan, J. J.; Liu, W. L.; Zhao, Y. J.; Sun, L. Y. Polydopamine decorated microneedles with Fe-MSC-derived nanovesicles encapsulation for wound healing. Adv. Sci. 2022, 9, 2103317.
Crossref Google Scholar
[43]

Aldhalimi, M. A.; Hadi, N. R.; Ghafil, F. A. Promotive effect of topical ketoconazole, minoxidil, and minoxidil with tretinoin on hair growth in male mice. ISRN Pharmacol. 2014, 2014, 575423.
Crossref Google Scholar
[44]

Maiorana, A.; O’Driscoll, G.; Taylor, R.; Green, D. Exercise and the nitric oxide vasodilator system. Sports Med. 2003, 33, 1013–1035.
Crossref Google Scholar
Nano Research
Volume 17 Issue 7,
July 2024
Pages 6411-6419
DOI: 10.1007/s12274-024-6619-0
Cite this article:
Chen H, Tang X, Huang Y, et al. Remodel the perifollicular microenvironment via Minoxidil-loaded microneedle patch and cold atmospheric plasma for treating androgenetic alopecia. Nano Research, 2024, 17(7): 6411-6419. https://doi.org/10.1007/s12274-024-6619-0
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Drug delivery

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Received: 21 January 2024
Revised: 06 March 2024
Accepted: 11 March 2024
Published: 04 April 2024
© Tsinghua University Press 2024
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