ABSTRACT
pH-sensitive polymerâ»liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymerâ»liposomes. In this study, stable and pH-sensitive crosslinked polymerâ»liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-cholesterol (mPEG-b-P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymerâ»liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG-b-P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymerâ»liposomes was approximately 140 nm and the polymerâ»liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymerâ»liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymerâ»liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymerâ»liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymerâ»liposomes offered a potent drug-delivery system for use in anticancer therapies.