In vitro evaluation of pH-sensitive polymer/niosome complexes.

ABSTRACT

Large unilamellar niosome and control liposome vesicles were rendered pH-sensitive by complexation with a hydrophobically modified pH-responsive copolymer of N-isopropylacrylamide, N-glycidylacrylamide, and N-octadecylacrylamide at a copolymer/lipid mass ratio of 0.3. The vesicles were characterized and tested for their stability and pH-sensitivity in buffer and human serum. Their in vitro cytotoxicity was evaluated as well as their ability to mediate cytoplasmic delivery of encapsulated fluorescent probe using J774 murine macrophage-like cells. At pH 7.2, vesicles were found to be stable over 90 days at 4 degrees C. At 37 degrees C, the polymer destabilized the vesicles under weakly acidic conditions. However, niosomes but not liposomes were partly destabilized in human serum at 37 degrees C. Premature leakage of niosomal contents in serum was attributed to the polymer collapse which is favored in the presence of multivalent cations. On the cellular level, niosomes were cytotoxic above 0.075 mM while no appreciable decrease in cell viability was shown for the liposomes and copolymer alone at short incubation times (< 2 days). Finally, only liposomes and not niosomes were able to release their contents in the cytoplasm after internalization by phagocytosis.