Amphiphilic copolymer for delivery of xenobiotics: in vivo studies in a freshwater invertebrate, a Mesostominae flatworm.

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de Jong, Laetitia | Moreau, Xavier | Thiery, Alain | Godeau, Guilhem | W. Grinstaff, Mark | Barthélémy, Philippe

Edité par CCSD ; American Chemical Society -

International audience. The synthesis of an amphiphilic polymethacrylate copolymer containing cholesterol hydrophobic moieties and rhodamine as a fluorescent probe, the formation of microspheres, and the uptake of these microspheres in an invertebrate are reported. The cholesterol-derived methacryloyl monomer, which was prepared via a one-step synthesis, was copolymerized with methacrylic acid and methacryloxyethyl thiocarbamoyl rhodamine B in the presence of AIBN as initiator. The obtained dye-labeled copolymer was characterized by (1)H NMR and UV-vis spectroscopy. Fluorescence and TEM microscopies studies show that this amphiphilic copolymer aggregates to give microspheres with diameters ranging from approximately 3 to 11 microm. The in vivo study in a freshwater invertebrate, a Mesostominae flatworm (Rhabdocoela, Thyphloplanidae), indicates that the microspheres enter the cells by endocytosis. The data collected demonstrate that the rhodamine B covalently attached to the amphiphilic copolymers is bioaccumulated without being translocated out of the cell by the multixenobiotic resistance (MXR) transporters. As the MXR system is similar to the multidrug resistance (MDR) first observed in tumor cell lines resistant to anticancer drugs, the present data confirm the significant role that amphiphilic copolymers can play in the ongoing development of drug delivery strategies to overcome multidrug resistance. These investigations illustrate a promising approach for the development of new medical and ecotoxicological tools that can deliver specific molecules within cells.

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