Serum-Stable, Long-Circulating, pH-Sensitive PEGylated Liposomes
pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of lysosomes. Serum-stable formulations with minimal leakage at physiological pH and rapid drug release at pH 5.0–5.5 can be easily prepared by inserting a hydrophobically modified N -isopropylacrylamide/methacrylic acid copolymer (poly(NIPAM-co -MAA)) in the lipid bilayer of sterically stabilized liposomes. The present chapter describes polymer synthesis, as well as the preparation, and characterization of large unilamelar pH-sensitive vesicles.
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