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

Abstract

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.