Center for Dermal Research (CDR), Rutgers-The State University of New Jersey, Piscataway, NJ 08854, United States; Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Int J Pharm. 2020 May 15;581:119278. doi: 10.1016/j.ijpharm.2020.119278. Epub 2020 Mar 27.
Berberine chloride (BBR) and evodiamine (EVO) are two main active ingredients of "ZuoJinWan", a classical Chinese herbal medicine, and these compounds are known to have a synergistic inhibitory effect on various cancer cell lines. Several recent studies have reported anti-melanoma effects for both BBR and EVO. However, topical delivery of the two compounds has been challenging, due to their poor aqueous solubility and their low skin penetration. In the current study, we have combined BBR and EVO into an ethosomes delivery system with the future aim to design a novel topical anti-melanoma formulation. The ethosomes formulations were characterized using particle size, entrapment efficiency and an in vitro skin drug deposition study. The ethosome formulation displaying maximum drug deposition in the epidermis was selected for further study. This formulation contained ethosomes with mean size of 171 nm and 90% or above entrapment efficiency for both BBR and EVO. Cell viability tests proved the optimized ethosomes increased the inhibitory effect on B16 melanoma cells. These results corroborate that ethosomes containing a combination of BBR and EVO are a promising delivery system for potential use in melanoma therapy.
盐酸小檗碱（BBR）和吴茱萸碱（EVO）是“左金丸”这一中草药的两种主要活性成分，这两种化合物对多种癌细胞系具有协同抑制作用。最近的几项研究报告称 BBR 和 EVO 均具有抗黑色素瘤作用。然而，由于其水溶性差和皮肤穿透性低，这两种化合物的局部递送一直具有挑战性。在本研究中，我们将 BBR 和 EVO 结合到醇质体传递系统中，以期设计一种新型的局部抗黑色素瘤制剂。采用粒径、包封率和体外皮肤药物沉积研究对醇质体制剂进行了表征。选择在表皮中具有最大药物沉积的醇质体制剂进行进一步研究。该制剂包含平均粒径为 171nm 的醇质体，BBR 和 EVO 的包封率均在 90%以上。细胞活力测试证明，优化后的醇质体增加了对 B16 黑色素瘤细胞的抑制作用。这些结果证实，含有 BBR 和 EVO 的醇质体是一种很有前途的黑色素瘤治疗传递系统。
