Sodium hyaluronate microcapsules to promote antitumor selectivity of anacardic acid

Anacardic acid (AA) is a phenolic lipid extracted from cashew nutshell liquid that has antitumor activity. Given the high hydrophobicity of this compound and aiming to create efficient vehicle for its administration in aqueous systems, the objective of the present work was to develop a microcapsule (MCAA) by spray dryer technique, based on the polysaccharide sodium hyaluronate (SH), containing AA as its core, encapsulated from nanoemulsion. The Encapsulation Efficiency of MCAA presented a value equal to 95.06 ± 1.22 %. In vitro release kinetic study showed a pH-responsive release, with greater release of AA from MCAA at pH 6.8 and 7.4 and almost none at pH 4.5, which prevents its delivery to the cellular lysosome. Tests on zebrafish did not show acute toxicity within 96 h or change in locomotor activity. The IC₅₀ determined in the MTT assay for the formulation presented values of 30.1 and 29.8 μg mL^-1 in HCT-116 and HL-60 cells, respectively, and did not present a detectable IC₅₀ in the concentration range tested for non-tumoral L-929 cells. Thus, encapsulation with sodium hyaluronate polysaccharide allowed a reduced toxicity in these cells compared to non-encapsulated AA (IC₅₀ = 0.70 μg mL^-1, in L-929), maintaining the inhibition of cancer cell growth. These results suggest adverse effects reduction, making MCAA promising for future applications in antineoplastic therapies.