A high stable pH-temperature dual-sensitive liposome for tuning anticancer drug release

In order to improve the targeting and availability of liposomes to cancer cells,the temperature sensitivity of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine(DPPC)and the pH sensitivity of PASP in PASP-g-C8 are incorporated in a drug delivery system.A composite pH-temperature dual-sensitive liposomes(CPTLPs)was obtained as an efficient drug delivery system.The bionic bilayer is self-assembled by cholesterol/cationic temperature-sensitive lipids as base layer and pH-sensitive octylamine grafted poly aspartic acid(PASP-g-C8)as anchors coated outside.Cytarabine(CYT)was chosen as a model drug.SEM and DLS were used to observe the morphology characteristics of CPTLPs in different micro environment.The results demonstrated that the CPTLPs remained active in both normal(pH7.4 and 37°C)and tumor tissues(pH 5.0 and 42°C).As a stable colloidal system,the zeta potential of CPTSLs was−41.6 mV.In vitro drug-release experiments,the CTY encapsulated dual-sensitive liposomes,CPTSLs(+),not only have significant pH-temperature sensitivity but have more prolonged release in vitro than control groups.MTT tests results indicated that the cell apoptotic effects induced by CPTSLs(+)were nearly 30%higher than the naked drug CTY in HepG2 cells,and 20%lower apoptotic in vero cells.The CPTSLs(+)sustained a stable emulsion form,less toxic effects on normal cells,and exhibited a good pH-temperature sensitivity,thus expected to be a promising tumor targeting drug delivery.