Controlled release of raloxifene by nanoencapsulation: effect on in vitro antiproliferative activity of human breast cancer cells

摘要

Abstract: Raloxifene hydrochloride (RH) is considered to be an antiproliferative agent of mammary tissue. The aim of this study was to investigate the effect of the encapsulation of RH in polymeric nanocapsules with anionic or cationic surface on its release profile and antiproliferative activity. They were prepared by interfacial deposition of preformed polymer, followed by wide physicochemical characterization. The in vitro RH release was assessed by the dialysis membrane method and the data analyzed by mathematical modeling. The antiproliferative effect on MCF-7?cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as well as by counting viable cells. They had high encapsulation efficiency, low polydispersity, and nanometric mean size. Nanocapsules prepared with Eudragit? RS100?and Eudragit? S100?presented positive and negative zeta potentials, respectively. Drug release studies demonstrated controlled release of RH from anionic nanocapsules, which could be explained due to a stronger interaction of the drug to these nanocapsules and the larger amount of entrapped drug. On the other hand, this control was not observed from cationic nanocapsules due to the larger amount of drug adsorbed onto their surface. MCF-7?cell viability studies and cell counting showed that RH-loaded Eudragit? RS100?nanocapsules promote the best antiproliferative activity after 24?hours of treatment, whereas the best activity was observed for RH-loaded Eudragit? S100?nanocapsules after 72?hours. Furthermore, the combined treatment of these formulations improved the antiproliferative effect during the entire treatment.