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Pharmaceutics · 2022 ·Vol. 14 ·期 7 ·1404 · IF 6.525

Promotion of Hair Regrowth by Transdermal Dissolvable Microneedles Loaded with Rapamycin and Epigallocatechin Gallate Nanoparticles

Yali Lin,Ruomei Shao,Tong Xiao,Shuqing Sun

Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of rapamycin and epigallocatechin gallate nanoparticles that can significantly promote hair regeneration. Compared with the mice without any treatment, our strategy can facilitate hair growth within 7 days. Higher hair shaft growth rate and hair follicle density with inconspicuous inflammation were exhibited in C57BL/6 mice, elucidating its potential for clinical application.Keywords:hair regrowth;microneedles;nanoparticles;rapamycin

CAS / MDL: 989-51-5
研究领域: 药理学 · 皮肤科学
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Advanced Composites and Hybrid Materials · 2025 ·Vol. 8 ·期 2 ·1-17 · IF 21.8

Glutamic acid-loaded separable microneedle composite for long-acting hair regeneration treatment

Mbituyimana Bricard,Fu Lina,Wang Hao,Qi Fuyu,Jiang Yuchi,Meng Fanbo,Wu Min,Shi Zhijun,Yang Guang

Androgenetic alopecia (AGA) is the most common type of hair loss frequently observed in clinics. Right now, there are no effective treatments for AGA. Here, we developed a biodegradable microneedle (MN) patch made of polylactic-co-glycolic acid (PLGA) loaded with glutamic acid (GA) that improves sustainable drug release and effective hair regeneration treatment. Once the patch has penetrated the skin, the GA-loaded MNs (GA-MNs) are quickly separated from their base and enter the skin. These MNs then serve as drug storage tanks inside the skin, releasing the therapeutics gradually for over 4 weeks. The sustained release of GA from long-acting biodegradable needles could lead to endocytosis by dermal papilla cells (DPCs), promoting the proliferation of cells. Compared with topical minoxidil, which requires daily treatment, animal studies have shown that GA-MNs can increase hair regeneration more effectively with lower dose frequency; the number of hair follicles in the GA-MNs group reached 83.68 ± 4.52%, which was significantly higher than that of the minoxidil group (56.93 ± 3.21%). This transdermal technology of biodegradable MNs shows considerable promise in clinical applications and offers a straightforward, safe, and effective therapy approach for clinical hair regeneration treatment.

CAS / MDL: 38304-91-5
研究领域: 生物医学工程 · 皮肤病学 · 药物递送系统
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2025 · IF 2.2

MafB regulates hair follicle stem cell activation and hair regeneration through NFATc1 signaling pathway

Qiuni Gao,Shangyu Zeng,Yupeng Chen,Ying Bao,Haiyan Cui

Alopecia, a prevalent condition driven by abnormal hair follicle cycling and stem cell (HFSCs) dysregulation, underscores the need to elucidate molecular mechanisms governing HFSCs activation. While the nuclear factor of activated T cells c1 (NFATc1) is known to maintain HFSCs quiescence by suppressing cyclin-dependent kinase 4 (CDK4), the upstream regulators of this pathway remain unclear. Here, we identify MafB as a key modulator of HFSCs dynamics through NFATc1 signaling. Transcriptome sequencing of murine skin revealed elevated MafB expression during active hair regeneration. Adenoviral overexpression of MafB in depilated mice accelerated hair regrowth, increased hair follicle diameter, and enhanced HFSCs proliferation. Conversely, MafB knockdown suppressed regeneration and reduced the prolifiration ability of HFSCs. In vitro , MafB overexpression promoted HFSCs proliferation, migration, and differentiation, while mechanistic studies demonstrated MafB inhibits NFATc1 transcription, thereby relieving CDK4 repression and activating Wnt/β-catenin signaling. Rescue experiments confirmed NFATc1 restoration abrogated MafB-induced HFSCs activation. These findings establish MafB as a critical regulator of hair follicle cycling through the NFATc1/CDK4 axis, offering novel therapeutic avenues for alopecia.

研究领域: 分子生物学 · 发育生物学 · 皮肤科学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Dissolving Microneedle Patch Integrated with Microspheres for Long-Acting Hair Regrowth Therapy

Meirong Yin,Yongnian Zeng,Han-Qing Liu,Wen Zhang,Chenyuan Wang,Chuang Chen,Wei Li

Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients’ self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.

CAS / MDL: 38304-91-5 142-55-2
研究领域: 药学 · 生物医学工程 · 皮肤科
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ZOOLOGICAL RESEARCH · 2024 ·Vol. 45 ·期 6 ·1287 · IF 4

Peptide Cy RL-QN15 accelerates hair regeneration in diabetic mice by binding to the Frizzled-7 receptor

Yu-Tong Wu,Ze-Qiong Ru,Ying Peng,Zhe Fu,Qiu-Ye Jia,Zi-Jian Kang,Yuan-Sheng Li,Yu-Bing Huang,Sai-Ge Yin,Kun Guo,Nai-Xin Liu,Cheng-An Feng,Jing Tang,Bai-Yu Zhang,Zhi Yang,Ying Wang,Xin-Wang Yang

Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide, Cy RL-QN15 , on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming (KM) mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy RL-QN15 treatment. Further analysis indicated that the hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.

研究领域: 糖尿病研究 · 伤口愈合 · 干细胞生物学 · 肽疗法 · 分子生物学
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MACROMOLECULAR BIOSCIENCE · 2025 · IF 4.1

Nitric Oxide Donor and Minoxidil Co-Loaded Microneedles Improving Hair Loss Treatment

Xueyang Wang,Xiaojie Ju,Chunyan He

The local application of minoxidil tincture has been widely used clinically for the treatment of androgenetic alopecia (AGA). However, there are significant limitations, including ineffectiveness on its own, poor patient compliance, and low transdermal absorption. Microneedles (MNs) can puncture the stratum corneum painlessly and increase drug absorption through the skin. Additionally, nitric oxide (NO) has been shown to improve blood supply to hair follicles and reduce inflammation. Therefore, we prepared a kind of hair-growth-promoting MNs that can co-deliver minoxidil and NO donor for AGA treatment. In simple terms, nanogels (MHMA) were formed through the photopolymerization of methacrylate hyaluronic acid (MeHA) and methacrylate arginine (MeArg) as an NO donor. Through optimized formulation design, minoxidil was efficiently encapsulated within the MHMA nanogels with a particle size of 522.9 nm, which facilitates targeting of hair follicles. Subsequently, the MNs were prepared using a micro-molding method. Both in vitro and in vivo experiments demonstrated that the hair-growth-promoting MNs could efficiently deliver minoxidil and NO donor by just 3 min pressing on the mouse skin. It effectively promoted the transition of hair follicles to the growth phase and stimulated angiogenesis around the follicles, ultimately leading to hair regeneration in the alopecia mouse model. Overall, the proposed hair growth hair-growth-promoting MNs can efficiently and painlessly deliver minoxidil and NO donor into the skin, thus offering a promising new direction for clinical AGA treatment.

研究领域: 药剂学 · 皮肤科 · 纳米技术 · 药物递送 · 生物医学工程
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Co-delivery of minoxidil and tocopherol acetate ethosomes to reshape the hair Follicular Microenvironment and promote hair regeneration in androgenetic alopecia

Aqin Yan,Rui Ruan,Xiaolei Zhu,Wei Qiang,Yeneng Guan,Qi Yu,Hongmei Sun,Mingxing Liu,Hongda Zhu

The most prevalent kind of hair loss is androgenic alopecia (AGA), which is characterized by hair follicle miniaturization and microenvironment dysfunction. Although topical Minoxidil (MXD) was considered to be a safe and effective treatment for AGA, excess reactive oxygen species (ROS) and lower sulfotransferase activity in the hair follicular microenvironment led to an unsatisfactory treatment of AGA. Here, we developed the ethosome (MTE) load of minoxidil and tocopherol acetate to improve the therapeutic effect of MXD on androgenic alopecia. It could regulate the microenvironment around hair follicles, promote the telogen-to-anagen transition of hair follicles, and boost hair regeneration, thus achieving a synergistic effect of 1 + 1 > 2. The results proved that MTE showed excellent stability, biosafety, and good dermal and follicular permeability in vitro . The hair regeneration ability of AGA model mice showed that the co-delivery ethosome might regulate the microenvironment around the hair follicles and improve hair regeneration in comparison to the commercial minoxidil tincture alone. As a result, the strategy provided a promising new strategy for the treatment of AGA.

研究领域: 药学 · 皮肤科 · 药理学
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Bioactive Materials · 2024 · IF 18

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment

Yan-Wen Ding,Yang Li,Zhi-Wei Zhang,Jin-Wei Dao,Dai-Xu Wei

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

研究领域: 药学 · 生物医学工程 · 皮肤科 · 材料科学 · 药物递送系统
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment

Xiaochuan Wu,Xiajie Huang,Qi Zhu,Jucong Zhang,Jiahao Hu,Yanling Song,Yuchan You,Luwen Zhu,Jingyi Lu,Xinyi Xu,Minjiang Chen,Wei Wang,Xiuzu Song,Jiansong Ji,Yongzhong Du

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

CAS / MDL: 10199-89-0 16961-25-4
研究领域: 皮肤科 · 纳米技术 · 干细胞生物学 · 药学
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Materials Today Advances · 2022 · IF 9.918

Harnessing a biopolymer hydrogel reinforced by copper/tannic acid nanosheets for treating bacteria-infected diabetic wounds

Shengye You,Yajing Xiang,Xiaoliang Qi,Ruiting Mao,Erya Cai,Yulong Lan,Hongyang Lu,Jianliang Shen,Hui Deng

Current diabetic wound treatments remain difficult in clinical due to bacterial infection and excessive reactive oxygen species (ROS). An ideal wound dressing should have prominent antibacterial and ROS scavenging abilities. In this work, a conveniently multifunctional hydrogel wound dressing (abbreviated as CuTA/SG) was constructed by incorporating copper/tannic acid nanosheets into a dynamic cross-linking network composed of oxidized sodium alginate, gelatin, and Ca 2+ . The resulting CuTA/SG hydrogel had excellent exudate absorption, adjustable photothermal antibacterial, and ROS scavenging features. Furthermore, CuTA/SG hydrogel was injectable that possessed excellent adaptability to adapt to the wound defects due to its appropriate physical cross-linking. Astonishingly, CuTA/SG hydrogel showed good hemostasis, antibacterial, anti-inflammation, and even hair regeneration capabilities, which can significantly promote diabetic wound healing in the full-thickness skin defect model in rats through reducing inflammation, guiding wound repair, and restoring skin physiological functions. Therefore, this study develops a simple and effective strategy for fabricating highly effective hydrogel dressing, which might provide new options for clinical wound management.

CAS / MDL: 7447-39-4 1401-55-4
研究领域: 材料科学 · 生物医学工程 · 药学 · 伤口愈合 · 纳米技术
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Nanoparticle Adjuvants Incorporating Haptens Drive Potent Immune Tolerance to Accelerate Hair Regrowth

Ni An,Guzailinuer Yasen,Ximu Li,Xianbao Shi,Yongjun Wang,Hongzhuo Liu

Alopecia areata (AA) is a prevalent autoimmune condition that causes sudden hair loss and poses significant psychological challenges to affected individuals. Current treatments, including corticosteroids and Janus kinase inhibitors, fail to provide long-term efficacy due to adverse effects and relapse after cessation. This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration. The results demonstrated that the coassembled NPs exhibited uniformity and stability, were efficiently taken up by antigen-presenting cells (APCs), and successfully induced dendritic cells (DCs) to differentiate into tolerogenic phenotypes in vitro. In vivo studies on a mouse model of alopecia showed that these NPs significantly accelerated the transition of hair follicles from the telogen phase to the anagen phase, promoting hair regrowth. This research presents a promising therapeutic strategy for AA and offers insights into treating autoimmune diseases where autoantigens are unclear.

研究领域: 免疫学 · 皮肤科 · 药学 · 自身免疫疾病
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Microneedle Delivery Platform Integrated with Codelivery Nanoliposomes for Effective and Safe Androgenetic Alopecia Treatment

Shuting Zhang,Hong Zhou,Xuan Chen,Shasha Zhu,Dan Chen,Dan Luo,Siyuan Chen,Wei Liu

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, β-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.

研究领域: 药学 · 纳米技术 · 皮肤科 · 生物医学工程
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