title: Paclitaxel-loaded micelles enhance transvascular permeability and retention of nanomedicines in tumors.
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.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, 73, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhier
authors.affiliation: Université catholique de Louvain, Institut de recherche expérimentale et clinique (IREC), Pole of Pharmacology, Avenue Mounier, 53, B1 53.09, 1200 Brussels, Belgium.
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: De Saedeleer
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, 73, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Fruytier
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schleich
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: des Rieux
authors.affiliation: Université catholique de Louvain, Institut de recherche expérimentale et clinique (IREC), Pole of Pharmacology, Avenue Mounier, 53, B1 53.09, 1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Laboratory of Biomedical Magnetic Resonance, Avenue Mounier, 73, B1 73.08, 1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D050997:Nanomedicine; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D013997:Time Factors; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D008823:Micelles; D011108:Polymers; D017239:Paclitaxel
keywords: EPR effect; Nanomedicine; Paclitaxel; Polymeric micelles; Tumor targeting; Tumor vasculature