Desenvolvimento de nanocápsulas poliméricas contendo curcumina e óleo de soja e avaliação toxicológica em linhagens celulares de câncer de próstata lncap e fibroblastos 3t3

Abstract

In Brazil, prostate cancer is the second most common type of cancer among men. For those diagnosed with metastatic disease or who develop it later, the therapeutic options are limited. Currently, natural compounds have been studied as therapeutic agents for the treatment of cancer, among which curcumin (CUR) is a potential chemotherapeutic for the treatment of prostate cancer. However, its low solubility and free form availability limit its use, requiring the use of delivery strategies, such as nanocapsules (NC), to overcome these problems. In this context, the aim of this work was the development of NC containing CUR and them cytotoxic evaluation in vitro. NC were prepared by the interfacial deposition of preformed polymer method using poly (ε-caprolactone) as polymer and soybean oil as oily core. A high performance liquid chromatography method was validated for quantification of CUR in NC and on in vitro release assays using dialysis method. The cytotoxic evaluation was performed against the LNCaP prostate cancer cell line. In addition, cytotoxicity and free and nanoencapsulated curcumin were evaluated in 3T3 fibroblast cell line. The encapsulation efficiency and drug content presented values of 70% and 0.45 mg.mL- 1 , respectively. The NC presented an average size of 257.6 ± 4.26 nm for NC without the drug (NCFree) and 276.3 ± 0.68 nm for NC containing the drug (NCCur). The zeta potential presented negative values of -29.35 ± 2.72 mV for NCFree and -28.38 ± 1.85 mV for NCCur. ThepH values were 5.5 for both formulations. The in vitro release assay demonstrated a inicial fast release (10% in 5 min) phase of CUR from the NC followed by a slow and sustained release phase (19% in 72h). The NC did not present genotoxicity, but presented cytotoxicity when submitted to the highest tested concentration (5ug.mL-1 ) on an exposure period of 72h. Regarding cytotoxicity in LNCaP prostate cancer cell line, both NCFree and NCCur significantly reduced the viability of tumor cells. This reduction was dependent on concentration and time of exposure. The NC containing soybean oil, with or without CUR, showed in vitro antitumor activity in prostate cancer in the tested concentrations, and could be considered as potential chemotherapeutic agents for cancer therapy.