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Paclitaxel (PTX)-loaded polymeric micelles (M-PTX) have been shown to enhance the blood flow and oxygenation of tumors 24 h 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 24 h 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.