COLL 548 |
| R. K. Prud'homme, Princeton U, Dept. of Chemical Engineering, Princeton, NJ 08544-5263 and Debra Auguste, Department of Chemical Engineering, Princeton University, Engineering Quadrangle, Princeton, NJ 08016. |
| The reversible association of electrostatically-modified PEG for endocytotic delivery of condensed DNA for gene therapy is presented. The major advantage of liposomal delivery is the fact that it separates the various functions required for successful gene delivery and therefore allows more flexibility than alternate strategies. Two types of polymers are being investigated: comb-graft polymers, where a PEG chain and an anchor is repeated, and single-tailed polymers, where multiple binding sites occur in series followed by a PEG chain. Our strategy is to increase the association of PEG to liposomes by incorporating multiple, relatively weak anchors to produce strong cooperative binding, but to be able to disassociate the PEG polymer from the liposome surface by a pH shift from pH 7.4 in the circulatory system to pH 5.5 in the endosome. Liposomes with varying electrostatic composition are prepared from mixtures of negatively charged DOPG, positively charged DOTAP, zwitterionic DOPC, and DODAP (which has a pKa of 6.7 and can change from neutral to positive under acidic conditions). The electrostatically bound PEG chains can be released from the liposome surface by the pH shift. This permits liposomal fusion in the endosome and release of the DNA contents. |
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“Smart” Polymers on Surfaces and Colloids
2:00 PM-4:50 PM, Thursday, April 1, 2004 Marriott -- Grand Ballroom J, Oral
Division of Colloid and Surface Chemistry |