In vitro characterization of a novel polymeric-based pH-sensitive liposomesystem

This study demonstrates rapid and pH-sensitive release of a highly water-so luble fluorescent aqueous content marker, pyranine, from egg phosphatidylch oline liposomes following incorporation of N-isopropylacrylamide (NIPA) cop olymers in liposomal membranes. The pH-sensitivity of this system correlate s with the precipitation of the copolymers at acidic pH. In vitro release c an be significantly improved by increasing the percentage of anchor in the copolymer and thus favoring its binding to the liposomal bilayer. In the ca se of liposomes containing a poly(ethylene glycol)-phospholipid conjugate, the insertion of the pH-sensitive copolymer in the liposomal membrane appea rs to be sterically inhibited. Dye release from these formulations at acidi c pH can still be achieved by varying the anchor molar ratio and/or molecul ar mass of the polymers or by including the latter during the liposome prep aration procedure. Removal of unbound polymer results in decreased leakage only when the copolymer is inserted by incubation with preformed liposomes, but can be overcome by preparing liposomes in the presence of polymer. Aqu eous content and lipid mixing assays suggest contents release can occur wit hout membrane fusion. The results of this study indicate that the addition of pH-sensitive copolymers of NIPA represents promising strategy for improv ing liposomal drug delivery. (C) 2000 Elsevier Science B.V. All rights rese rved.