Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex

J Nanobiotechnology. 2016 Feb 19:14:11. doi: 10.1186/s12951-016-0163-3.

Abstract

Background: Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post-menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects.

Objectives: The aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy.

Methods: A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of tamoxifen and forming 'LPPC/TAM' for transdermal release. The cytotoxicity of LPPC/TAM was analyzed by MTT. The skin penetration, tumor growth inhibition and organ damages were measured in xenograft mice following transdermal treatment.

Results: LPPC/TAM had an average size less than 270 nm and a zeta-potential of approximately 40 mV. LPPC/TAM displayed dramatically increased the cytotoxic activity in all breast cancer cells, especially in ER-positive breast cancer cells. In vivo, LPPC drug delivery helped the fluorescent dye penetrating across the skim and accumulating rapidly in tumor area. Administration of LPPC/TAM by transdermal route inhibited about 86 % of tumor growth in mice bearing BT474 tumors. This local treatment of LPPC/TAM did not injury skin and any organs.

Conclusion: LPPC-delivery system provided a better skin penetration and drug accumulation and therapeutic efficacy. Therefore, LPPC/TAM drug delivery maybe a useful transdermal tool of drugs utilization for breast cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Breast / drug effects
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Delivery Systems / methods
  • Female
  • HEK293 Cells
  • Humans
  • Liposomes / administration & dosage*
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Polyethylene Glycols / administration & dosage
  • Polyethyleneimine / administration & dosage
  • Polyethyleneimine / analogs & derivatives
  • Tamoxifen / administration & dosage*

Substances

  • Liposomes
  • poly(ethylene glycol)-co-poly(ethyleneimine)
  • Tamoxifen
  • Polyethylene Glycols
  • Polyethyleneimine