Design, characterization and in vitro evaluation of linalool-loaded solid lipid nanoparticles as potent tool in cancer therapy

Abstract

Linalool (LN) is a monoterpene found in essential oils of plants and herbs that producesmultiple effects on the mevalonate pathway and interesting antiproliferative activity incancer cells. However, due to its poor aqueous solubility, an efficient vehicle is needed toimprove its administration and bioavailability in physiological media.LN encapsulation in solid lipid nanoparticles (SLN) with different compositions was exploredand in vitro tested in two cancer cell lines. SLN of myristyl myristate (MM), cetyl esters (SS)and cetyl palmitate (CP) were prepared by sonication in the presence of Pluronic®F68 assurfactant. Nanoparticle size, morphology and distribution were determined by dynamic lightscattering in combination with optical and transmission electron microscopy (TEM). SLNshowed spherical shape and mean diameters in the range of 90-130 nm with narrow sizedispersion (PDI values lower than 0.2) and Z potentials around -4.0 mV. The encapsulationpercentages of LN in SLN were higher than 80% for all tested formulations and exhibited invitro LN controlled release profiles for at least 72 h. The nanoparticles were physicochemicallycharacterized by FTIR, XRD, DSC and TGA, and the incorporation of LN into SLN was higherthan 80% in tested matrices. The developed formulations, and in particular SLN (MM)-LN,showed in vitro antiproliferative effects on hepatocarcinoma (HepG2) and lungadenocarcinoma (A549) cell lines in a dose-dependent response, and higher inhibitory effectswere found in comparison with free LN. The cellular uptake of SLN was demonstrated byfluorescence microscopy, enhancing the ability of nanoparticles to intracellularly deliver thecargo molecules.