Increased resistance of DNA lipoplexes to protein binding in vitro by surface-modification with a multivalent hydrophilic polymer.
The potential of cationic liposomes as DNA delivery vehicles for gene therapy is significantly limited by their instability upon systemic administration. Their strong positive charge induces non-specific binding of serum proteins and subsequent clearance from the circulation. This work investigates the ability of the multivalent reactive copolymer of poly[N-(2-hydroxypropopyl) methacrylamide], pHPMA (MA-GG-ONp) to shield lipoplexes from non-specific protein binding. The polymer was found to react with cationic liposome-DNA complexes (lipoplexes) in both an electrostatic and covalent manner to form an external polymer coat. Polymer coating resulted in an increase in lipoplex diameter (by up to 100 nm) that was proportional to the amount of polymer used, with a concomitant reduction in surface charge from strongly positive to neutral (from 30 to 0 mV). Polymer-coated lipoplexes exhibited increased stability to protein binding compared to untreated liposomes and reduced non-specific uptake into cells in vitro.
Papanicolaou
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Centre for Drug Delivery Research, The School of Pharmacy, University of London, London, UK.
Briggs
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Alpar
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D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013499:Surface Properties
D008081:Liposomes; D011108:Polymers; D004247:DNA