PEG-b-PCL Copolymer Micelles with the Ability of pH-Controlled Negative-to-Positive Charge Reversal for Intracellular Delivery of Doxorubicin

• DOI: 10.1021/bm501290t
• Publication Date: 2014-10-17T18:37:41Z
• Authors: Hongzhang Deng; Jinjian Liu; Xuefei Zhao; Yuming Zhang; Jianfeng Liu; Shuxin Xu; Liandong Deng; Anjie Dong; Jianhua Zhang
• Keywords: Gel permeation chromatography

The application of PEG-b-PCL micelles was dampened by their inherent low drug-loading capability and relatively poor cell uptake efficiency. In this study, a series novel copolymers methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-γ-dimethyl maleamidic acid -ε-caprolactone) (mPEG-b-P(CL-co-DCL)) bearing different amounts acid-labile β-carboxylic amides on the polyester moiety were synthesized. chain structure chemical composition characterized (1)H NMR, Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC). mPEG-b-P(CL-co-DCL) with critical micellar concentrations (CMCs) 3.2-6.3 μg/mL could self-assemble into stable in water diameters 100 to 150 nm. Doxorubicin (DOX), cationic hydrophobic drug, successfully encapsulated polymer micelles, achieving very high loading content due electrostatic interaction. Then stability, charge-conversional behavior, release profiles, cellular vitro cytotoxicity free drug drug-loaded evaluated. functionalized are negatively charged neutral solution but quickly become positively at pH 6.0, hydrolysis acidic conditions. pH-triggered negative-to-positive charge reversal not only resulted fast conditions, also effectively enhanced absorptive endocytosis. MTT assay demonstrated that biocompatible HepG2 cells while DOX-loaded showed significant cytotoxicity. sum, introduction block exhibited great potentials for modifications stability blood circulation, solubilization, properties, as well internalization intracellular release.