Desenvolvimento de nanodispersões líquido cristalinas contendo Doxorrubicina e avaliação da citotoxidade em linhagem celular de câncer de próstata

Abstract

Nanotechnology is increasingly present in the pharmacological field, being responsible for optimizing therapies, among them the treatment of cancer. Many drugs used in cancer therapy are very toxic, bringing serious side effects and decreasing the quality of life of the patient during treatment. The nanotechnology applied to cancer treatment comes as an alternative to reduce these effects, making the treatment optimized, while potentiating the toxic effects of antineoplastic drugs, reduces its deleterious effects, by better directing the treatment to the target of the disease. Since most of these nanocarriers are of lipid origin, they cross biological membranes better, improving the bioavailability of the drug. Among these drugs, doxorubicin (DOX) is one of the most widespread, being used in the treatment of several types of cancer by inhibiting RNA synthesis in cancer cells. Doxorubicin, on the other hand, is very cytotoxic, causing cardiotoxicity, myelosuppression, kidney, and liver problems. Seeking strategies to reduce these effects, causing a better efficiency in the treatment, it was decided to use nanotechnology to encapsulate doxorubicin in liquid crystals based on monolein (MO) and PHOSAL® (PHO), a lipid mixture containing phosphatidylcholine. The development of crystals was done by means of a phase diagram to determine the proportion of the formulation components, observing liquid crystals with a hexagonal phase. After dispersion of the liquid crystals in a probe sonicator, nanoparticles were obtained with an average size of 344.9 nm ± 4.133, polydispersity index of 0.396 ± 0.015, encapsulation efficiency of 99.76% and zeta potential of -14.7 mV ± 0.321. The method for quantification of doxorubicin was spectrophotometric, which was validated and proved suitable for the study. In the evaluation of cytotoxicity against human prostate cancer lineage cells (PC3), an IC50 value of 1.003 ± 0.185 µM was obtained for the doxorubicin solution and IC50 of 2.116 ± 0.233 µM for the doxorubicin nanodispersion. Given this context, the present study achieved its main objective, to develop and characterize liquid crystals containing doxorubicin and demonstrate its potential to be used as a nanocarrier of the drug in therapy for prostate cancer cells, thus agreeing with other studies published in scientific literature.