The Institute of Drug Research of the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Plastic and Reconstructive Surgery, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Int J Pharm. 2023 Jul 25;642:123121. doi: 10.1016/j.ijpharm.2023.123121. Epub 2023 Jun 10.
Over the years, extensive research has been carried out to develop new chemical entities for hair loss treatment. Despite these efforts, the newly developed topical and oral treatments have not proven to be curative. Hair loss can result from underlying mechanisms, such as inflammation and apoptosis around hair follicles. We have developed a nanoemulsion based on Pemulen gel for topical application, tentatively addressing both mechanisms. The novel formulation contains two well-known molecules: Cyclosporin A (CsA), an immunosuppressant calcineurin inhibitor, and Tempol, a potent antioxidant. The in vitro permeation study on human skin revealed that the CsA-Tempol gel formulation effectively delivered CsA into the skin's inner target layer, the dermis. The effects of the CsA-Tempol gel on hair regrowth were further demonstrated in the in vivo well-established androgenetic model induced in female C57BL/6 mice. The beneficial outcome was statistically confirmed by quantitative analysis of hair regrowth, measured by color density. The results were further supported by histology analysis. Our findings revealed a topical synergy effect, resulting in lower therapeutic concentrations of both actives unlikely to cause systemic side effects. Overall, our research suggests that the CsA-Tempol gel is a highly promising platform for treating alopecia.
多年来,人们进行了广泛的研究,以开发用于脱发治疗的新化学实体。尽管有这些努力,新开发的局部和口服治疗方法并未被证明是治愈性的。脱发可能是由于潜在的机制引起的,例如毛囊周围的炎症和细胞凋亡。我们开发了一种基于 Pemulen 胶的纳米乳液,用于局部应用,初步针对这两种机制。该新型制剂包含两种知名分子:环孢素 A(CsA),一种免疫抑制剂钙调神经磷酸酶抑制剂,和 Tempol,一种有效的抗氧化剂。在人体皮肤上的体外渗透研究表明,CsA-Tempol 凝胶制剂可将 CsA 有效递送至皮肤的内层靶层真皮。CsA-Tempol 凝胶对毛发再生的影响在体内建立的雌性 C57BL/6 小鼠诱导的雄激素性脱发模型中进一步得到证实。通过颜色密度测量的毛发再生的定量分析,对有益的结果进行了统计学确认。组织学分析进一步支持了这些结果。我们的研究结果揭示了一种局部协同作用,导致两种活性剂的治疗浓度降低,不太可能引起全身副作用。总体而言,我们的研究表明,CsA-Tempol 凝胶是治疗脱发的极具前景的平台。