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 produces multiple effects on the mevalonate pathway and interesting antiproliferative activity in cancer cells. However, due to its poor aqueous solubility, an efficient vehicle is needed to improve its administration and bioavailability in physiological media. LN encapsulation in solid lipid nanoparticles (SLN) with different compositions was explored and 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 as surfactant. Nanoparticle size, morphology and distribution were determined by dynamic light scattering in combination with optical and transmission electron microscopy (TEM). SLN showed spherical shape and mean diameters in the range of 90-130nm with narrow size dispersion (PDI values lower than 0.2) and Z potentials around -4.0mV. The encapsulation percentages of LN in SLN were higher than 80% for all tested formulations and exhibited in vitro LN controlled release profiles for at least 72h. The nanoparticles were physicochemically characterized by FTIR, XRD, DSC and TGA, and the incorporation of LN into SLN was higher than 80% in tested matrices. The developed formulations, and in particular SLN (MM)-LN, showed in vitro antiproliferative effects on hepatocarcinoma (HepG2) and lung adenocarcinoma (A549) cell lines in a dose-dependent response, and higher inhibitory effects were found in comparison with free LN. The cellular uptake of SLN was demonstrated by fluorescence microscopy, enhancing the ability of nanoparticles to intracellularly deliver the cargo molecules.

Keywords: Cancer cells; Cellular uptake; Cytotoxicity; Drug delivery; Linalool solid lipid nanoparticles.