Paclitaxel-loaded micelles enhance transvascular permeability and retention of nanomedicines in tumors

Int J Pharm. 2015 Feb 20;479(2):399-407. doi: 10.1016/j.ijpharm.2015.01.009. Epub 2015 Jan 8.

Abstract

Paclitaxel (PTX)-loaded polymeric micelles (M-PTX) have been shown to enhance the blood flow and oxygenation of tumors 24h after treatment. We hypothesized that these changes in the tumor microenvironment could lead to an enhancement of the EPR (enhanced permeability and retention) effect. M-PTX, administered 24h before analysis, increased the accumulation of macromolecules, nanoparticles and polymeric micelles in tumors. This increased EPR effect could be linked to normalization of the tumor vasculature and decreased interstitial fluid pressure. M-PTX used as a pre-treatment allowed a more effective delivery of three nanomedicines into tumors: polymeric micelles, liposomes and nanoparticles. These experiments demonstrate an enhanced EPR effect after M-PTX treatment, which lead to better availability and enhanced efficacy of a subsequent treatment with nanomedicines.

Keywords: EPR effect; Nanomedicine; Paclitaxel; Polymeric micelles; Tumor targeting; Tumor vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Female
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • Nanomedicine
  • Nanoparticles*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacology
  • Permeability
  • Polymers / chemistry
  • Time Factors
  • Tumor Microenvironment / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • Micelles
  • Polymers
  • Paclitaxel