Insertion of pH-sensitive bola-type copolymer into liposome as a "stability anchor" for control of drug release

How to design intelligent carriers for delivering drugs to the target accurately and releasing drug timely with the help of a certain environmental stimulus is still a challenge in tumor treatment. In this work, pH-sensitive bola-type triblock copolymers, composed of poly(2-(diisopropylamino) ethylmethacrylate) (PDPA) and methoxy-poly(ethyleneglycol) (mPEG), were synthesized. Liposomes containing these copolymers (Liposome@Bola) have been prepared by simply mixing the copolymer with phospholipids and cholesterol. From the fluorescence polarization measurement, the stability of Liposome@Bola was found to be increased a lot comparing to the pure liposome. As a result, the doxorubicin (DOX) leakage of the former was restrained in neutral environment. However, when pH decreased from 7.4 to 6.0, DOX released percentage had been increased 30-60 points, which was heavily depend on the phospholipid composition. Furthermore, the size effects of PEG and PDPA segments were also investigated. These results indicated the synthesized bola-type copolymers improved the pH-controllability of drug release of liposome, i.e., increased the difference between the release amount under pH 7.4 and pH 6.0. The bola-type copolymer exhibited a good potential application in smartly controlling drug delivery system.