4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 512, Issue 1, Pages 22-31

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2016.08.038

Keywords

(-)-Epigallocatechin-3-O-gallate; Nanoethosomes; Transdermal delivery; Docetaxel; Skin cancer; Pharmacokinetics

Funding

  1. Fund for Distinguished Scholars of Zhejiang Agricultural and Forestry University [2014FR064]
  2. National Natural Science Foundation of China [31270724]
  3. National Key Technology RD Program [2012BAD36B06]
  4. Natural Science Foundation of Zhejiang Province [LZ12C16004]

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(-)-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. (C) 2016 Elsevier B.V. All rights reserved.

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