Bioactive Molecules Research Laboratory, Faculty of Sciences, Lebanese University, Lebanon; Laboratoire d'Automatique, de Génie des Procédés et de Génie Pharmaceutiques (LAGEPP), Université Claude Bernard Lyon 1, France.
UMR 1098 RIGHT INSERM EFS BFC, DImaCell Imaging Ressource Center, University of Bourgogne Franche-Comté, Besançon, 25000, France.
Eur J Pharm Sci. 2022 Jan 1;168:106082. doi: 10.1016/j.ejps.2021.106082. Epub 2021 Nov 22.
Skin hyperpigmentation is caused by an excessive production of melanin. Cysteamine, an aminothiol compound physiologically synthetized in human body cells, is known as depigmenting agent. The aim of this study was to evaluate the depigmenting activity and skin penetration of liposome formulations encapsulating cysteamine hydrochloride. First, cysteamine hydrochloride-loaded liposomes were prepared and characterized for their size, polydispersity index, zeta potential and the encapsulation efficiency of the active molecule. The stability of cysteamine hydrochloride in the prepared liposome formulations in suspension and freeze-dried forms was then assessed. The in vitro cytotoxicity of cysteamine and cysteamine-loaded liposome suspensions (either original or freeze-dried) was evaluated in B16 murine melanoma cells. The measurement of melanin and tyrosinase activities was assessed after cells treatment with free and encapsulated cysteamine. The antioxidant activity of the free and encapsulated cysteamine was evaluated by the measurement of ROS formation in treated cells. The ex vivo human skin penetration study was also performed using Franz diffusion cell. The stability of cysteamine hydrochloride was improved after encapsulation in liposomal suspension. In addition, for the liposome re-suspended after freeze-drying, a significant increase of vesicle stability was observed. The free and the encapsulated cysteamine in suspension (either original or freeze-dried) did not show any cytotoxic effect, inhibited the melanin synthesis as well as the tyrosinase activity. An antioxidant activity was observed for the free and the encapsulated cysteamine hydrochloride. The encapsulation enhanced the skin penetration of cysteamine hydrochloride. The penetration of this molecule was better for the re-suspended freeze-dried form than the original liposomal suspension where the drug was found retained in the epidermis layer of the skin.
皮肤色素沉着是由于黑色素的过度产生引起的。半胱胺，一种在人体细胞中生理合成的氨硫醇化合物，是一种脱色剂。本研究旨在评估包封盐酸半胱胺的脂质体制剂的脱色活性和皮肤穿透性。首先，制备盐酸半胱胺负载的脂质体并对其粒径、多分散指数、zeta 电位和活性分子的包封效率进行了表征。然后评估了在悬浮液和冻干形式的制备脂质体制剂中盐酸半胱胺的稳定性。在 B16 小鼠黑色素瘤细胞中评估了游离半胱胺和载有半胱胺的脂质体混悬液（原始或冻干）的体外细胞毒性。用游离和包封的半胱胺处理细胞后，测量黑色素和酪氨酸酶活性。通过测量处理细胞中 ROS 的形成，评估游离和包封的半胱胺的抗氧化活性。还使用 Franz 扩散细胞进行了离体人皮肤渗透研究。盐酸半胱胺的稳定性在包封在脂质体混悬液中后得到改善。此外，对于冻干后再悬浮的脂质体，观察到囊泡稳定性显著增加。游离和包封的半胱胺在混悬液中（原始或冻干）均无细胞毒性作用，抑制黑色素合成和酪氨酸酶活性。观察到游离和包封的盐酸半胱胺具有抗氧化活性。包封增强了盐酸半胱胺的皮肤穿透性。这种分子的穿透性对于再悬浮的冻干形式更好，而原始的脂质体混悬液中药物被发现保留在皮肤的表皮层中。
