pH-responsive and biodegradable polymeric micelles based on poly(β-amino ester)-graft-phosphorylcholine for doxorubicin delivery

Abstract

The pH-triggered biodegradable micelles based on poly(β-amino ester)-graft-12-acryloyloxy dodecyl phosphorylcholine (PAE-graft-ADPC) were explored as an efficient acid-triggered anticancer drug delivery system. A pH-responsive biodegradable polymer was synthesized by using hydrophilic 12-acryloyloxy dodecyl phosphorylcholine (ADPC) and poly(β-amino ester) (PAE) via Michael addition reaction. Micelles with phosphorylcholine shells were prepared in aqueous solution and doxorubicin (DOX) was loaded into the core of the micelles with high efficiency (73%). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated that the size of the drug-loaded micelles was about 230 nm. DOX-loaded micelles were stable in the physiological environment, whereas they disassembled at pH 6.5 which is similar to the extracellular pH of most tumors. In vitro drug release showed that DOX release from micelles was faster at pH 6.5 than at 7.4. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles at pH 6.5. Moreover, an in vitro cytotoxicity study indicated that the growth of HepG2 cells was inhibited remarkably when the cells were preincubated with DOX-loaded micelles at pH 6.5. The results indicated that the pH-triggered biodegradable micelles could serve as promising drug carriers for cancer therapy.