Dutasteride, licensed as an oral medicine for the treatment of benign prostatic hypoplasia, has been investigated as a treatment for androgenic alopecia. In this study, the potential for dustasteride to be delivered topically in order to reduce systemic exposure, irritation of the skin, and also cytotoxicity was explored. Chitosan oligomer (CSO) was successfully synthesised with lauric acid as a coating for a dutasteride-loaded nanostructured lipid carriers (DST-NLCs) system. DST-NLCs were prepared using a combination of melt-dispersion and ultrasonication. These negatively charged NLCs (−18.0 mV) had a mean particle size of ~184 nm, which was not significantly increased (p > 0.05) when coated with lauric acid-chitosan oligomer (CSO-LA), whilst the surface charge changed to positive (+24.8 mV). The entrapment efficiency of DST-NLCs was 97%, and coated and uncoated preparations were physically stable for up to 180 days at 4–8 °C. The drug release was slower from DST-NLCs coated with CSO-LA than from uncoated NLCs, with no detectable drug permeation through full-thickness pig ear skin from either preparation. Considering the cytotoxicity, the IC₅₀ values for the DST-NLCs, coated and uncoated with CSO-LA were greater than for dutasteride alone (p < 0.05). DST-NLCs and empty NLCs coated with CSO-LA at 25 µM increased the cell proliferation compared to the control, and no skin irritation was observed when the DST-NLC formulations were tested using EpiDerm™. The cell and skin uptake studies of coated and uncoated NLCs incorporating the fluorescent marker Coumarin-6 showed the time-dependent uptake of Coumarin-6. Overall, the findings suggest that DST-NLCs coated with CSO-LA represent a promising formulation strategy for dutasteride delivery for the treatment of androgenic alopecia, with a reduced cytotoxicity compared to that of the drug alone and lower irritancy than an ethanolic solution of dutasteride.

中文翻译：

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月桂酸-壳聚糖低聚物包覆的度他雄胺-纳米结构脂质载体用于皮肤输送的体外性能


度他雄胺被许可作为治疗良性前列腺发育不全的口服药物，已被研究用于治疗雄激素性脱发。在这项研究中，探讨了局部给药布斯雄胺以减少全身暴露、皮肤刺激以及细胞毒性的潜力。使用月桂酸成功合成了壳聚糖低聚物（CSO）作为负载度他雄胺的纳米结构脂质载体（DST-NLC）系统的涂层。 DST-NLCs 采用熔融分散和超声处理相结合的方式制备。这些带负电的 NLC (-18.0 mV) 的平均粒径约为 184 nm，当涂有月桂酸-壳聚糖低聚物 (CSO-LA) 时，粒径没有显着增加 ( p > 0.05)，而表面电荷变为正（+24.8 mV）。 DST-NLC 的包封率为 97%，包衣和未包衣制剂在 4–8 °C 下物理稳定长达 180 天。涂覆有 CSO-LA 的 DST-NLC 的药物释放速度比未涂覆的 NLC 慢，两种制剂均未检测到药物渗透过猪耳全层皮肤。考虑到细胞毒性，用 CSO-LA 包被和未包被的 DST-NLC 的 IC ₅₀值均大于单独的度他雄胺 ( p < 0.05)。与对照相比，涂有 25 µM CSO-LA 的 DST-NLC 和空 NLC 增加了细胞增殖，并且当使用 EpiDerm™ 测试 DST-NLC 配方时没有观察到皮肤刺激。掺有荧光标记香豆素 6 的涂层和未涂层​​ NLC 的细胞和皮肤吸收研究表明，香豆素 6 的吸收具有时间依赖性。 总体而言，研究结果表明，涂​​有 CSO-LA 的 DST-NLC 代表了一种有前途的用于治疗雄激素性脱发的度他雄胺递送制剂策略，与单独药物相比，其细胞毒性降低，并且比度他雄胺乙醇溶液的刺激性更低。