PH-Sensitive biodegradable PMAA2-b-PLA-b-PMAA2 H-type multiblock copolymer micelles: synthesis, characterization, and drug release applications

Abstract

pH-Sensitive biodegradable polymethacrylic acid-block-polylactic acid-block-polymethacrylic acid (PMAA2-b-PLA-b-PMAA2) H-type multiblock copolymers were synthesized by atom transfer radical polymerization. The copolymer structure and molecular weight were characterized by FT-IR, 1H NMR, and gel permeation chromatography. The physicochemical characterization revealed that the copolymers could spontaneously form spherical core–shell micelles in aqueous solution, with critical aggregation concentration of about 19.7–32.5 mg L−1 and the hydrodynamic diameters below 200 nm. Zeta potentials measurements disclosed that the copolymer micelles were negatively charged due to ionized carboxyl groups in various PBS solutions. The H-type block copolymer micelles exhibited pH- sensitivity, as expected; and the hydrophobic anticancer drugs, 10-hydroxycamptothecin, and paclitaxel, had faster release rate in PBS solution of pH 5.6–7.4 than in PBS of pH 1.4, which was important for applications in the therapy of small intestine cancers. The copolymer micelle aggregates were proved to be biodegradable, and the degradation rates changed with copolymer compositions and environmental media. The micelle drug formulation indicated pH-dependent cytotoxicity and was thus capable of effectively killing the intestinal cells while avoiding doing harm to stomach. The biodegradable pH-sensitive PMAA2-b-PLA-b-PMAA2 H-type copolymer micelles can be used as water-insoluble drug targeting release carriers for targeted treatment of intestine cancers.