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• W2007276486 abstract "Anionic pH-sensitive membrane-disruptive polymers have evolved as a new class of bioactive excipients for the cytosolic delivery of therapeutic macromolecules. A large variety of anionic copolymers and analogues of poly(acrylic acid) (PA) was investigated and compared to a cationic PA copolymer. The pH-responsive membrane-disruptive properties were characterized by employing three in vitro models, such as pH dependent shift of pyrene fluorescence, liposome leakage and lysis of red blood cells. The pH-dependent increase of polarity and membrane disruption in the different model systems was in good agreement for all tested PA polymers. The efficacy of polymer-induced membrane disruption was concentration-dependent and significantly affected by the composition of the membrane. The sensitivity of relatively complex membranes of mammalian cells can be ranked between plain diphosphatidylcholine (DPPC) liposomal membranes and the more rigid cholesterol-containing DPPC membranes. Among the various studied PA polymers, medium and low molecular poly(ethacrylic acid) (PEA) and poly(propacrylic acid) (PPA) were identified as displaying significant pH-dependent disruptive activity. Relative to the disruptive cationic PA polymer (PDMAEM) the ranking is PEA < PPA < PDMAEM. The fine tuning of the pH-responsive hydrophilic-hydrophobic balance is likely to be responsible for the superior effect of PEA and PPA compared to other anionic PA polymers. This thorough investigation of a large variety of different anionic PA polymers and the comparison with an efficient, although rather toxic cationic PA polymer provides a good assessment for further therapeutic applications." @default.
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• W2007276486 date "2003-09-01" @default.
• W2007276486 modified "2023-10-13" @default.
• W2007276486 title "Evaluation of pH-dependent membrane-disruptive properties of poly(acrylic acid) derived polymers" @default.
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• W2007276486 doi "https://doi.org/10.1016/s0939-6411(03)00093-6" @default.
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