Anionic polyethyleneglycol lipids added to cationic lipoplexes increase their plasmatic circulation time

Cationic liposomes have been widely sensed as good DNA compacting delivery agents. Although their use generally met with encouraging results in vitro, the results in vivo were rather disappointing as them strongly interact with the blood components before them can reach the therapeutic target. Polyethyleneglycol (PEG) shielding has been proposed a,, a ay to alleviate this effect. but was still found unsatisfactory in most instances for, systemic administration. We demonstrate here that the insertion of anionic functions between the lipid part and the PEG. at a correct distance to favor electrostatic interactions with the outer cationic layer of the lipoplexes. provides not only a decrease in the mean peripheral charge of the lipoplex ( zeta potential). but also a greater colloidal stability of the particles in the presence of serum. Transfection in the lung is also decreased with negatively charged PEG shielding. although no significant changes are observed in the tumor. This encouraging new approach should consequently be combined with active extra-cellular receptor targeting to achieve the desired delivery of the therapeutic DNA to tumor tissues. (C) 2003 Elsevier Science B.V. All rights reserved.