Abstract：
Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.
摘要：
斑秃（AA）是一种慢性自身免疫性疾病，其特征是身体某些区域的秃斑，尤其是头皮.米诺地尔(MNX),作为AA的一线治疗，有效诱导头发生长。然而,口服和局部给药带来问题，包括低生物利用度，不受控制的头发生长的风险，和局部副作用，如燃烧脱发，和头皮刺激。在最新的研究中,MNX通过微针(MN)经皮递送至皮肤。MNX浓度分布在整个针中,使得药物渗透减少并且具有刺激的可能性。在这项研究中,我们将MNX配制成三层溶解微针（TDMN）以增加药物渗透并避免刺激。物理化学评价,parafilm,用于评估TDMN的机械强度，并表明TDMN可以穿透角质层。离体渗透测试表明,对于TDMN2获得最高的平均渗透结果,即165.28±31.87ug/cm2,而对于米诺地尔乳膏,其为46.03±8.5ug/cm2。离体和体内皮肤动力学测试的结果表明,与乳膏制剂相比,来自TDMN2配方的皮肤中残留的药物浓度的量更高。根据HET-CAM测试和溶血测试，开发的配方没有潜在的刺激和毒性。TDMN是施用MNX以克服MNX问题并增加AA治疗的有效性的有希望的替代方案。
