Desenvolvimento de nanocarreadores lipídicos contendo ácido retinóico para o tratamento de câncer

Abstract

The antitumor drugs have poor specificity, high toxicity and adverse reactions. The targeting of these agents loaded in nanostructured systems to the tumor region can overcome such drawbacks. The vitamin A (retinol) derivatives such as all-trans retinoic acid (RA), a lipophilic drug (log P equal to 4.6) may be used in the treatment of several cancer types, especially leukemia. The lipid nanocarriers, nanoemulsions (NE) and solid lipid nanoparticles (SLN) are particularly interesting systems forlipophilic drugs such as RA. Therefore, the objective of this study was to develop, characterize and evaluate the antitumor activity of NE and SLN loaded with RA for the treatment of cancer. The in situ formation of an ion pairing between RA and an amine was investigated as an alternative for increased retention in the lipid matrix. NE loaded with RA and stearylamine (SA) or triethylamine (TA) and SLN loaded with RA and SA, TA or benethamine (BA) were developed. The presence of amines significantly increased the encapsulation efficiency of RA in both nanocarriers. The in vitro cytotoxic activity of RA encapsulated in the lipid carriers was higher than the RA free, and the NLS promoted the highest increase in this activity than the NE. Formulations containing SA loaded or not with RA were cytotoxic to normal and cancer cells. Among the amines chosen, BA was the one that promoted the highest increase in cytotoxic activity and the retention of RA in the lipid matrix of the SLN over time. Taken together, these findings suggest that the RA-BA-loaded SLN are apromising alternative to intravenous administration of RA in the cancer treatment.