DataSheet1_Bioengineered polyester nanoparticles for the synergistic treatment of androgenic alopecia via the suppression of 5α-reductase and knockdown of androgen receptor.docx

Androgenic alopecia (AGA) is a common disease that negatively affects patients’ physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The in vitro study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the in vivo study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.

雄激素性脱发（Androgenic alopecia, AGA）是一类常见疾病，会对患者的身心健康造成负面影响。目前临床可通过改善毛囊周围微环境的药物治疗AGA，例如5α-还原酶抑制剂（如度他雄胺[dutasteride, DUT]）、雄激素受体拮抗剂以及米诺地尔，但此类治疗手段的疗效较为有限。因此，本研究旨在验证纳米颗粒作为稳定载体的有效性，其不仅具备较高的治疗获益，且不良反应轻微。
体外研究结果显示，PLGA-DUT/siAR@DPCM纳米粒（NPs）可同时将DUT与siAR递送至真皮乳头细胞，分别有效抑制5α-还原酶活性并敲低雄激素受体的表达，进而促进细胞增殖。
体内研究表明，在AGA小鼠模型中，PLGA-DUT/siAR@DPCM纳米粒展现出显著的治疗效果：其可顺利穿透角质层，并对毛囊及周围组织呈现明确的靶向作用。
PLGA-DUT/siAR@DPCM纳米粒可通过经皮递送途径实现DUT与siAR的靶向递送，增强细胞吞噬作用并降低不良反应，因此在AGA的临床治疗中具备巨大应用潜力。