Acta Biomater:米诺地尔-透明质酸-溶解微针减轻脱发动物模型的脱发研究

2022-03-31 医路坦克 MedSci原创

本研究表明透明质酸减少了脱发小鼠的脱发,使用米诺地尔-透明质酸-微针输送米诺地尔和透明质酸可以最大限度地发挥疗效,并将米诺地尔治疗脱发的副作用降至最低。

    大多数脱发是由睾酮引起的,睾酮是雄激素的一种,通过5-α-还原酶将其转化为二氢睾酮。这一过程导致毛囊角质形成细胞的凋亡,端原排泄增加,毛发周期缩短,毛囊缩小。

    透明质酸(HA)和毛囊之间的关系需要广泛的研究,因为它占据很大一部分。HA(一种GAG蛋白)的表达水平在休止期毛囊中降低。HA还有助于发展重要的角质形成细胞活性,包括细胞粘附和增殖。此外,据报道HA水平随着脱发的进展而降低

    在用于治疗脱发的药物中,如非那雄胺、度他雄胺和氟他胺(口服药物),以及米诺地尔(MXD,只有两种药物,非那雄胺和MXD已获得食品和药物管理局(FDA)的批准。MXD作为一种血管舒张剂和钾通道开放剂,可以延长生长期并扩大小卵泡。然而,由于头皮对局部MXD的吸收率仅为1.4%,因此必须长期反复使用;因此,必须每天两次涂在皮肤上至少4个月才能治疗脱发。因此,由于吸收率低和治疗时间长的缺点,只有不到40%的患者对治疗有反应。尽管皮内注射MXD能够有效地增加分娩,但它们伴随着疼痛,导致长期治疗期间的不依从。为了克服这些缺点并提高MXD的疗效,需要新的药物配方和新的皮内给药系统。

    角质层强大的屏障功能是药物吸收不良的主要原因之一。使用激光选择性去除角质层或对皮肤脂质具有高亲和力的化学增强剂可以增加药物吸收,这些皮肤脂质在物理和化学上改变角质层的结构。脂质体已被用于通过毛囊递送药物,据报道醇质体可促进MXD的皮肤渗透性。纳米粒子还可以通过穿透分流途径(如头发折叠)来输送药物。然而,所有这些方法都有局限性,因为它们可能引起皮肤刺激和损伤,并且稳定性差和不希望的全身吸收。

   为了开发一种治疗脱发的新平台,我们采用了可溶可生物降解的MNS。我们选择HA作为MN的材料,MN在毛发周期和脱发中受到调节。尽管已有大量研究表明HA对细胞功能的影响,如对其他细胞的增殖、迁移和黏附的影响,但其对毛细胞的影响还没有完全确定。在这项研究中,我们验证了HA对HDP细胞毛发形成特性的有利影响,并探讨了相关机制。在化疗诱导的脱发动物模型上,测试了MXD的控释作用,并观察了含有MXD的HA-MNS对毛发生长的影响,并与MXD局部应用进行了比较。

    为了克服低吸收,我们建议将微针(MNS)作为释放MXD的受控给药系统。我们使用透明质酸(HA)构建MN,因为它具有生物相容性和安全性。我们检测了HA对控制毛囊发育的毛乳头(HDP)细胞的影响。HA通过增加细胞间黏附和减少细胞底物促进HDP细胞的增殖、迁移和聚集。这些作用是通过分化簇(CD)-44和丝氨酸苏氨酸激酶(Akt)的磷酸化来实现的。在化疗诱导的脱发小鼠中,局部应用HA往往能减少化疗导致的脱发。虽然HA-MNS的MXD用量是外用MXD的10%,但含有MXD的HA-MNS(MXD-HA-MNS)对毛发生长的影响比MXD外用更好。

    综上所述,我们的结果表明,HA减少了脱发小鼠的脱发,使用MXD-HA-MNS输送MXD和HA可以最大限度地发挥疗效,并将MXD治疗脱发的副作用降至最低。

文献来源:Kim MJ,  Seong KY,  Kim DS, Minoxidil-loaded hyaluronic acid dissolving microneedles to alleviate hair loss in an alopecia animal model.Acta Biomater 2022 Feb 21;

 

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    2022-06-26 windight
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    2023-03-10 sunylz
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    2022-03-31 14700d17m84暂无昵称

    学习

    0

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    2022-03-31 仁术2021

    不错学习了

    0

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