(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line

Int J Mol Sci. 2020 Feb 20;21(4):1449. doi: 10.3390/ijms21041449.

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.

Keywords: (+)-limonene 1,2-epoxide; HaCaT cell line; Imwitor 900K-SLN; cytotoxicity; lipid peroxidation; monoterpene.

MeSH terms

  • Antioxidants* / chemistry
  • Antioxidants* / pharmacokinetics
  • Antioxidants* / pharmacology
  • Cell Line
  • Cyclohexane Monoterpenes* / chemistry
  • Cyclohexane Monoterpenes* / pharmacokinetics
  • Cyclohexane Monoterpenes* / pharmacology
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Humans
  • Keratinocytes / metabolism*
  • Lipid Peroxidation / drug effects*
  • Monoglycerides* / chemistry
  • Monoglycerides* / pharmacokinetics
  • Monoglycerides* / pharmacology
  • Nanoparticles / chemistry*
  • Poloxamer* / chemistry
  • Poloxamer* / pharmacokinetics
  • Poloxamer* / pharmacology

Substances

  • Antioxidants
  • Cyclohexane Monoterpenes
  • Delayed-Action Preparations
  • Monoglycerides
  • Poloxamer
  • limonene-1,2-epoxide