Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer

J Drug Target. 2015 Feb;23(2):159-69. doi: 10.3109/1061186X.2014.965717. Epub 2014 Sep 30.

Abstract

Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

Keywords: Anticancer; glycery monostearate; oxidative stress; pharmacodynamics; topical.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use*
  • Apoptosis / drug effects
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / chemistry
  • Benzodioxoles / therapeutic use*
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Design
  • Drug Stability
  • HL-60 Cells
  • Humans
  • Male
  • Mice, Inbred Strains
  • Nanoparticles / chemistry*
  • Particle Size
  • Phenols / administration & dosage
  • Phenols / chemistry
  • Phenols / therapeutic use*
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin Absorption
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Surface Properties

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Benzodioxoles
  • Drug Carriers
  • Phenols
  • sesamol