Nanoemulsão à base de óleo de Calotropis procera contendo ácido betulínico para aplicação contra câncer de próstata

Abstract

A major difficulty in using conventional drugs in cancer treatment is related to their hydrophobicity in biological systems. An alternative to overcome this problem is the encapsulation of drugs through nanotechnology, such as nanoemulsions. In this work, an oil-in-water nanoemulsion formulation based on Calotropis procera seed oil containing betulinic acid (BA) was developed for use against prostate cancer. The physicochemical characterization of C. procera oil was performed by determining its viscosity index, iodine value, acidity value and saponification index. A study of the colloidal stability of the formulated nanoemulsion was also carried out by evaluating the particle size, zeta potential, polydispersity index and quantification of the active ingredient. The results showed that the produced nanoemulsion was stable at temperatures of 25 °C and 45 °C for 90 days. The components of the nanoemulsion (C. procera oil, betulinic acid and Pluronic F127) were characterized by FTIR and NMR. The cell viability of tumor cell lines was evaluated by the MTT test. In vivo toxicity tests were performed in a zebrafish model. The release kinetics and mechanisms were evaluated by in vitro release tests. The nanoemulsion showed high BA carrying capacity (7500 μg/mL), thermodynamic stability and high encapsulation efficiency (99.98%). Tests in zebrafish revealed that the nanoemulsion did not alter locomotor activity and did not present acute toxicity within 96 h of oral administration. In the 72-h in vitro release test, it presented controlled release by the Higuchi model, releasing 31.33% (622.80 μg) of BA in a controlled manner. The NE-F2.2 formulation showed cytotoxic activity for all tumor cell lines, with the most expressive inhibition for PC3 cells (human prostate carcinoma) with IC50 of 4.6 to 6.2 μg/mL and > 75 μg/mL for fibroblasts. Therefore, the proposed formulation proved to be stable in the tests of stability, biological safety and controlled release of BA, showing promise as an antitumor drug, specifically prostate cancer.