Curcumin Nanoemulsions Stabilized with Modified Phosphatidylcholine on Skin Carcinogenesis Protocol

Curr Drug Metab. 2020;21(3):226-234. doi: 10.2174/1389200221666200429111928.

Abstract

Background: Cancer is one of the main causes of death by disease; several alternative treatments have been developed to counteract this condition. Curcumin (diferuloylmethane), extracted from the rhizome of Curcuma longa, has antioxidant, anti-inflammatory, and anti-cancer properties; however, it has low water solubility and poor intestinal absorption. Carrier systems, such as nanoemulsions, can increase the bioavailability of lipophilic bioactive compounds.

Objective: To evaluate the effect of curcumin nanoemulsions prepared with lecithin modified with medium-chain fatty acids as an emulsifier, on the expression of the Cdk4, Ccne2, Casp8 and Cldn4 genes involved in the carcinogenesis process in K14E6 transgenic mice.

Methods: The emulsifier was prepared by interesterification of medium-chain fatty acids, pure lecithin, and immobilized phospholipase-1 on Duolite A568. An Ultraturrax homogenizer and a Branson Ultrasonic processor were used for the preparation of nano-emulsions, and a Zetasizer evaluated the particle size. qRT-PCR analysis was performed to quantify the cancer-related genes expressed in the K14E6 mice. The development and evolution of skin carcinogenesis were assessed through histological analysis to compare cell morphology.

Results: Ca 59% of the MCFA were incorporated via esterification into the PC within 12 hours of the reaction. An emulsifier yield used to formulate the NE of 86% was achieved. Nanoemulsions with a particle size of 44 nm were obtained. The curcumin nano-emulsion group had a 91.81% decrease in the tumorigenesis index and a reduction in tumor area of 89.95% compared to the sick group. Histological analysis showed that the group administered with free curcumin developed a microinvasive squamous cell carcinoma, as opposed to the group with nanoemulsion which presented only a slight inflammation. In gene expression, only a significant difference in Cdk4 was observed in the nanoemulsion group.

Keywords: Curcumin; gene expression; histology; medium-chain fatty acids; modified lecithin; nano-emulsions; skin carcinogenesis..

MeSH terms

  • Animals
  • Biological Availability
  • Carcinogenesis / drug effects*
  • Caspase 8 / metabolism
  • Claudin-4 / metabolism
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclins / metabolism
  • Drug Compounding / methods*
  • Emulsions / chemistry
  • Lecithins
  • Mice
  • Mice, Transgenic
  • Nanoparticles / chemistry
  • Phosphatidylcholines / chemistry*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • CCNE2 protein, human
  • CLDN4 protein, human
  • Claudin-4
  • Cyclins
  • Emulsions
  • Lecithins
  • Phosphatidylcholines
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • CASP8 protein, human
  • Caspase 8
  • Curcumin