(-)-Epigallocatechin gallate (EGCG)-nanoethosomes as a transdermal delivery system for docetaxel to treat implanted human melanoma cell tumors in mice

Int J Pharm. 2016 Oct 15;512(1):22-31. doi: 10.1016/j.ijpharm.2016.08.038. Epub 2016 Aug 18.

Abstract

(-)-Epigallocatechin-3-O-gallate (EGCG), a versatile natural product in fresh tea leaves and green tea, has been investigated as a preventative treatment for cancers and cardiovascular disease. The objective of this study was to develop EGCG-nanoethosomes for transdermal delivery and to evaluate them for treating subcutaneously implanted human melanoma cell tumors. EGCG-nanoethosomes, composed of 0.2% EGCG, 2% soybean phosphatidylcholine, 30% ethanol, 1% Tween-80 and 0.1% sugar esters, were prepared and characterized using laser transmission electron microscopy. These nanoethosomes were smoother and more compact than basic-nanoethosomes with the same components except for EGCG. The effectiveness of transdermal delivery by EGCG-nanoethosomes was demonstrated in an in vitro permeability assay system using mouse skin. The inhibitory effect of docetaxel (DT) loaded in EGCG-nanoethosomes (DT-EGCG-nanoethosomes) was analyzed by monitoring growth of a subcutaneously implanted tumor from A-375 human melanoma cells in mice. Mice treated with DT-EGCG-nanoethosomes exhibited a significant therapeutic effect, with tumors shrinking, on average, by 31.5% of initial volumes after 14 d treatment. This indicated a potential for treating skin cancer. In a pharmacokinetic study, transdermal delivery by DT-EGCG-nanoethosomes enabled sufficient DT exposure to the tumor. Together, these findings indicated that EGCG-nanoethosomes have great potential as drug carriers for transdermal delivery.

Keywords: (−)-Epigallocatechin-3-O-gallate; (−)-Epigallocatechin-3-O-gallate (PubChem CID: 65064); Docetaxel; Docetaxel (PubChem CID: 148124); Nanoethosomes; Pharmacokinetics; Skin cancer; Transdermal delivery.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / chemistry
  • Catechin / pharmacokinetics
  • Catechin / pharmacology
  • Docetaxel
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Drug Stability
  • Female
  • Humans
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Permeability
  • Skin / metabolism*
  • Taxoids / chemistry
  • Taxoids / pharmacokinetics
  • Taxoids / pharmacology*
  • Transdermal Patch
  • Xenograft Model Antitumor Assays*

Substances

  • Drug Carriers
  • Taxoids
  • Docetaxel
  • Catechin
  • epigallocatechin gallate