title: Cytotoxicity and internalization of Pluronic micelles stabilized by core cross-linking.
abstract: A UV-cross-linkable agent was incorporated and polymerized in Pluronic micelle core to create an interpenetrating polymer network (IPN) of poly(pentaerythritol tetraacrylate). This stabilization prevented micelle disruption below the critical micelle temperature (CMT) and concentration (CMC), while maintaining the integrity of the PEO corona and the hydrophobic properties of the PPO core. The prepared stabilized spherical micelles of Pluronic P94 and F127 presented hydrodynamic diameters ranging from 40 to 50 nm. The stability of cross-linked Pluronic micelles at 37 °C in the presence of serum proteins was studied and no aggregation of the micelles was observed, revealing the colloidal stability of the system. Cytotoxicity experiments in NIH/3T3 mouse fibroblasts revealed that the presence of the cross-linking agent did not induce any further toxicity in comparison to the respective pure polymer solutions. Furthermore, stabilized micelles of Pluronic P94 were shown to be less toxic than the polymer itself. A hydrophobic fluorescent probe (Nile red) was absorbed in the cross-linked core of pre-stabilized micelles to mimic the incorporation of a poorly water-soluble drug, and the internalization and intracellular localization of Nile red was studied by confocal microscopy at different incubation times. Overall, the results indicate that Pluronic micelles stabilized by core cross-linking are capable of delivering hydrophobic components physically entrapped in the micelles, thus making them a potential candidate as a delivery platform for imaging or therapy of cancer.
authors.affiliation: Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034 Strasbourg Cedex 2, France. Electronic address: alexandra.arranja@ics-cnrs.unistra.fr.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Arranja
authors.affiliation: Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.
authors.forename: André P
authors.initials: AP
authors.lastname: Schroder
authors.affiliation: Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmutz
authors.affiliation: Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Waton
authors.affiliation: Institut Charles Sadron (UPR22-CNRS), 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.
authors.forename: François
authors.initials: F
authors.lastname: Schosseler
authors.affiliation: Dept Chemical Engineering, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mendes
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects*; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D010078:Oxazines; D020442:Poloxamer / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011409:Propylene Glycols
chemical_list: D001798:Blood Proteins; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D008823:Micelles; D010078:Oxazines; D011409:Propylene Glycols; D020442:Poloxamer; C044808:nile red; C008783:pentaerythritol
keywords: Block copolymer; Cytotoxicity; Micelle stabilization; Pluronic; Self-assembling; UV cross-linking