Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy

Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Ni...

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Main Authors: Hui Xing, Huanqi Peng, Yuhui Yang, Kai Lv, Shihao Zhou, Xiangjun Pan, Jianjin Wang, Yunfeng Hu, Guowei Li, Dong Ma
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-02-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X23003055
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author Hui Xing
Huanqi Peng
Yuhui Yang
Kai Lv
Shihao Zhou
Xiangjun Pan
Jianjin Wang
Yunfeng Hu
Guowei Li
Dong Ma
author_facet Hui Xing
Huanqi Peng
Yuhui Yang
Kai Lv
Shihao Zhou
Xiangjun Pan
Jianjin Wang
Yunfeng Hu
Guowei Li
Dong Ma
author_sort Hui Xing
collection DOAJ
description Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Nitric oxide (NO) is a signaling molecule in various physiological processes, including vasodilation, immune responses, and cell proliferation. Herein, we constructed a hyaluronic acid liposome (HL) complex as a novel transdermal delivery system (HL@Mi/NONOate) for NO and Mi, which displayed promising transdermal and hair-regrowth effects. In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy. First, NO promoted capillary dilation and accelerated blood flow, thus achieving efficient penetration of Mi. Due to the structural advantage of liposomes, the residence time of the Mi in the skin was prolonged. Moreover, HL@Mi/NONOate promoted cell proliferation and angiogenesis, and upregulated the expression of regulatory factors involved in follicle stem cell differentiation. In the AGA model, HL@Mi/NONOate down-regulated the expression of inflammatory factors, inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth. Concurrently, HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues, inducing follicle regeneration and development, ultimately achieving the synergistic multimodal AGA therapy.
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spelling doaj.art-e0bb39079e174b7ab142560c8e4d3f742023-11-27T04:15:02ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-02-0132190205Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapyHui Xing0Huanqi Peng1Yuhui Yang2Kai Lv3Shihao Zhou4Xiangjun Pan5Jianjin Wang6Yunfeng Hu7Guowei Li8Dong Ma9The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China; Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, ChinaThe First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, ChinaHonest Medical China Co., Ltd, Zhuhai, 519000, ChinaThe First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China; Corresponding author. The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China.The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China; Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China; Corresponding author. The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510630, China.Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China; MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, 510632, China; Corresponding author. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Nitric oxide (NO) is a signaling molecule in various physiological processes, including vasodilation, immune responses, and cell proliferation. Herein, we constructed a hyaluronic acid liposome (HL) complex as a novel transdermal delivery system (HL@Mi/NONOate) for NO and Mi, which displayed promising transdermal and hair-regrowth effects. In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy. First, NO promoted capillary dilation and accelerated blood flow, thus achieving efficient penetration of Mi. Due to the structural advantage of liposomes, the residence time of the Mi in the skin was prolonged. Moreover, HL@Mi/NONOate promoted cell proliferation and angiogenesis, and upregulated the expression of regulatory factors involved in follicle stem cell differentiation. In the AGA model, HL@Mi/NONOate down-regulated the expression of inflammatory factors, inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth. Concurrently, HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues, inducing follicle regeneration and development, ultimately achieving the synergistic multimodal AGA therapy.http://www.sciencedirect.com/science/article/pii/S2452199X23003055Nitric oxideLiposomeEnhanced penetrationSynergistic therapyAndrogenetic alopecia
spellingShingle Hui Xing
Huanqi Peng
Yuhui Yang
Kai Lv
Shihao Zhou
Xiangjun Pan
Jianjin Wang
Yunfeng Hu
Guowei Li
Dong Ma
Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
Bioactive Materials
Nitric oxide
Liposome
Enhanced penetration
Synergistic therapy
Androgenetic alopecia
title Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
title_full Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
title_fullStr Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
title_full_unstemmed Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
title_short Nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic-alopecia therapy
title_sort nitric oxide synergizes minoxidil delivered by transdermal hyaluronic acid liposomes for multimodal androgenetic alopecia therapy
topic Nitric oxide
Liposome
Enhanced penetration
Synergistic therapy
Androgenetic alopecia
url http://www.sciencedirect.com/science/article/pii/S2452199X23003055
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