Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal

Abstract

In Brazil, advances in science have allowed substances responsible for exhibiting antitumor activity to be isolated from native fauna and flora, such as anacardic acid (AA), extracted from the liquid from the shell of cashew nuts. However, this compound is hydrophobic, making it necessary to develop efficient vehicles for its administration in aqueous systems. In the literature, there are few studies that encapsulate AA in selective delivery systems for cancer treatment. Thus, the objective of the present work was to develop a microcapsule based on the polysaccharide sodium hyaluronate (HS), containing AA as the core, encapsulated from a nanoemulsion with licuri oil. For this, the nanoemulsion (NEAA) was obtained using the ultrasonication technique. The microcapsule (MCAA) was formed after adding NEAA to an aqueous solution of HS, followed by drying the resulting mixture using a spray dryer. The particle size of the aqueous redispersion of MCAA has a value of 292.1 ± 1.2 nm, suggesting that the polysaccharide encapsulation of the nanoemulsion was efficient and the zeta potential (-52.2 ± 1.2 mV) revealed an increase in stability parameters in relation to the nanoemulsion (- 29.7 ± 1.6 mV). MCAA presented an Encapsulation Efficiency value equal to 95.06 ± 1.22%. The Scanning Electron Microscopy revealed a spherical shape for the MCAA powder particles, with an average size of 3.7 ± 2.1 µm. The microcapsules achieved in vitro accumulated release of AA equal to 4.18 ± 0.75% at pH equal to 7.4, with a controlled release of AA in relation to the free active ingredient (27.33 ± 3.85%) and showed pH-responsive release, with a reduction in the percentage of AA at pH 6.8 (2.83 ± 0.39%) and pH 4.5 (0.18 ± 0.12%). In vivo tests did not produce acute toxicity in zebrafish or changes in locomotor activity after treatment with the formulation. The IC50 determined for the formulation presented values of 30.1 and 29.8 µg mL1 in HCT-116 and HL-60 tumor cells, respectively, and did not present a detectable IC50 in the concentration range tested for non-tumor L-929 cells. Thus, the AA encapsulation process through intermolecular interactions with licuri oil and later with HS allowed a reduction in toxicity in these cells compared to non-encapsulated AA (IC50 = 0.70 µg mL-1 in L-929), strongly suggesting a reduction in toxicity and possible side effects, being promising for future applications in cancer therapies.