(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line
Eliana B. Souto, Aleksandra Zielińska, Selma B. Souto, Alessandra Durazzo, Massimo Lucarini, Antonello Santini, Amélia M. Silva, Atanas G. Atanasov, Conrado Marques, Luciana Nalone Andrade, Patrícia Severino
Abstract
In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (Lim-SLNs), stabilized with Poloxamer® 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim-SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim-SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.