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Interaction between polyether- poly (2-dimethylaminoethyl methacrylate)copolymers and phospholipid model vesicles – implications for gene delivery efficiency

J.F. Tan, L. Bromberg, K.C. Tam, H.P. Too and T.A. Hatton
Singapore-MIT Alliance, SG

Keywords:
fluorescence anisotropy, copolymers of Pluronic and poly (2-dimethylaminoethyl methacrylate) (pDMA), phospholipids vesicles

Abstract:
Our previous studies have demonstrated that surface-active copolymers of Pluronic® surfactants and tertiary amino polycations such as poly (2-dimethylaminoethyl methacrylate) (pDMA) possess an enhanced DNA transfection efficiency compared to pDMA homopolymers. The transfection efficiencies of the Pluronic-pDMA gene carriers were strongly affected by the interaction between the polymer and cell membrane. In order to understand the mechanism of such action, we conducted model studies of the interaction of polymer with phospholipid vesicles and cell membranes. Three cationic methacrylate polymer systems were used in this study: pDMA homopolymer, and PEO-b-PDMA and Pluronic L92-b-pDMA block copolymers. The results from fluorescence anisotropy study (figure 1) and 5(6)-Carboxyfluorescein (CF) release assay (figure 2) showed that despite analogous chemical structures, the interaction mechanisms between the various polymers and phospholipids vesicles were significantly different. The pDMA and PEO-b-PDMA only interact with the surface of the vesicles, whereas L92-b-PDMA interacts strongly with the inner hydrophobic segment of the vesicles. The studies show that the strong interaction between L92-b-PDMA and phospholipid membrane could explain the enhanced transfection efficiency previously shown by the Pluronic L92-b-PDMA copolymer.

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