Summary : Cysteamine, an aminothiol compound synthetized by human body cells, presents several biological activities such as radioprotective and anticancer effects. It is the only treatment of cystinosis and can be used for Parkinson and Huntington treatments. This molecule also shows a depigmenting effect and has different forms like cysteamine hydrochloride. However, cysteamine is hygroscopic, presents poor organoleptic properties and pharmacokinetic profile. In addition, cysteamine is unstable in aqueous solutions because of its oxidation to its disulfide form cystamine. To overcome these problems, cysteamine and its hydrochloride form were encapsulated in liposomes, respectively. The liposomal suspensions were characterized for their size, homogeneity, zeta potential and the encapsulation efficiency of cysteamine and cysteamine hydrochloride were determined. The simultaneous quantification of cysteamine and cystamine by ion pair liquid chromatography was optimized. The stability of cysteamine and its hydrochloride form in the liposomes was also studied in different storage conditions. The freeze drying of the liposomal suspension was carried out to increase the shelf life of the formulations. The characterization after storage of the lyophilized form was also done. The liposomes were nanometric, monodisperse and a low encapsulation efficiency of the active product was obtained. The stability of cysteamine and cysteamine hydrochloride was increased after encapsulation especially after freeze-drying. Finally, the optimized formulations of cysteamine hydrochloride-loaded liposomes in liquid and dried forms were tested for their depigmenting effect. Their toxicity by the MTT assay, the dosage of melanin, the tyrosinase activity and the skin penetration of the free and the encapsulated cysteamine hydrochloride were evaluated. These tests showed that the selected formulations did not show cytotoxicity to the B16 murine melanoma cell line. Cysteamine hydrochloride and cystamine induced melanin and tyrosinase inhibition. Encapsulation of cysteamine decreased the effect of this inhibition but increased the penetration of the molecule into the skin and its retention in the epidermis. Cystamine did not penetrate and has not been found in skin layers.
Keywords: cysteamine, cystamine, ion pair chromatography, depigmenting effect, liposomes, freeze drying, skin penetration, stability.
Date(s) - 16 Dec 2020
14 h 00 min - 16 h 00 min
CatégoriesFiled under: Defense, GEPHARM