A pH/reduction dual-sensitive copolymer inserted in liposomal bilayer acts as a protective "umbrella"

Developing a targeted intelligent drug delivery system with excellent controllability of drug release remains an ongoing challenge in chemotherapy. A multistage responsive liposome was constructed by inserting a folate (FA) modified lipid and a pH/reduction dual-sensitive copolymer into the liposome bilayer. The properties of liposome were studied by fluorescence polarization, dynamic light scattering and in vitro drug release. Since the PDPA segment of the copolymer could embed in or escape from the liposomal bilayer depending on pH value, the membrane stability of the liposome was improved at pH 7.4 and decreased at pH 5.0. As a result, the drug leakage of the liposome was significantly suppressed at pH 7.4 but promoted at an acidic pH. Moreover, the liposome Lipo5-FA, which contained negatively charged FA groups protected by the longer PEG, was found to undergo membrane fusion with the positively charged Lipo( + ) to verify the longer PEG was cut by GSH. All results indicated that the smart copolymer acted as a switch on liposomal bilayer for drug release and also a protective "umbrella" for FA.