State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Jinhua Institute of Zhejiang University, Jinhua 321299, China.
State Key Laboratory of Advanced Drug Delivery and Release Systems, Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
J Control Release. 2024 Sep;373:652-666. doi: 10.1016/j.jconrel.2024.07.066. Epub 2024 Aug 1.
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.
雄激素性脱发（AGA）是一种全球性的非致命疾病。然而，不同的 AGA 患者毛发生长治疗方法的疗效存在差异。因此，通过毛囊干细胞（HFSC）衍生的细胞外囊泡与脂质体之间的膜融合，构建了一种基于混合细胞外囊泡包载金纳米粒子（AuNPs）和非那雄胺（Hybrid/Au@Fi）的协同治疗的纳米平台。这些混合囊泡（HVs）不仅通过细胞外囊泡提供细胞信号来促进毛发生长，而且还提高了储存稳定性、毛囊保留率和非那雄胺的包封效率（EE%），以抑制 5α-还原酶，并且纳米尺寸的 AuNPs 在体外模拟低水平激光治疗（LLLT）具有相似的光热效应。非那雄胺在这些 HVs 中的 EE%达到 45.33%。这些细胞外囊泡和非那雄胺的双重给药在体外对 HFSCs 表现出强烈的协同作用。在 AGA 小鼠模型中，每天一次局部施用 Hybrid/Au@Fi（115.07 ± 0.32nm，-7.50 ± 1.68mV）凝胶导致毛囊（HFs）更快地从退行期向生长期转变，增加了毛发生长的覆盖率，并提高了再生毛发的质量，与每天一次 5%米诺地尔治疗相比。与局部米诺地尔相比，通过局部给药的 Hybrid/Au@Fi 的多方面协同治疗为具有低副作用的难治性 AGA 患者提供了一种新的选择。
