微针输送平台与 Codelivery 纳米脂质体集成，可有效、安全地治疗雄激素性脱发,ACS Applied Materials & Interfaces

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微针输送平台与 Codelivery 纳米脂质体集成，可有效、安全地治疗雄激素性脱发
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-03-20 , DOI: 10.1021/acsami.3c16608
Shuting Zhang ₁ , Hong Zhou ₁ , Xuan Chen ₁ , Shasha Zhu ₁ , Dan Chen ₂ , Dan Luo ₂ , Siyuan Chen ₃ , Wei Liu _{1,

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Affiliation

虽然米诺地尔的局部应用是一种广泛使用的、经 FDA 批准的雄激素性脱发 (AGA) 治疗方法，但它存在生物利用度低、需要频繁长期使用以及副作用等问题。科培西和科吡咯与米诺地尔结构相似，毒性较小，已商品化，但与米诺地尔相比，毛发再生效果较差。在此，我们开发了一种基于透明质酸（HA）的可溶性微针（MN）递送平台，与科培西和科吡咯共封装纳米脂质体（KK-NLP）集成，以有效、安全地治疗 AGA。在纳米脂质体和 MN 的促进下，封装的 KK-NLP 能够有效地渗透皮肤并增强细胞内化到人真皮乳头细胞中。此外，在靶细胞内，共同递送的 kopexil 和 kopyrrol 通过协调 Ki67、β-连环蛋白、血管内皮生长因子 (VEGF) 和 CD31 的表达上调而显示出协同效应。这些分子反应共同促进细胞增殖、迁移和抗氧化作用，从而促进毛囊（HF）加速进入毛发生长初期阶段并促进外周血管生成。值得注意的是，整合 KK-NLPs 的 MNs 治疗组在体内表现出显着增强的毛发再生能力，在比米诺地尔低得多的剂量下具有相同或更好的治疗效果。这些结果表明，这种 kopexil 和 kopyrrol 共递送纳米脂质体集成 MN 平台在以安全有效的方式治疗 AGA 方面具有巨大潜力。

"点击查看英文标题和摘要"

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

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.

更新日期：2024-03-20

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