Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release

An amphiphilic star block copolymer comprised of a hydrophobic PMMA block and a hydrophilic tri-arm poly(NIPAAm-co-DMAEMA) block was synthesized by copolymerization of NIPAAm and DMAEMA, with Ce4+ ions and tris(hydroxymethyl)methylamine as a redox initiatory system. The star copolymer undergoes self-assembly to the micellar nanoparticles with a core–shell structure and the thermo/pH dual-response, originated from the thermo-sensitivity of PNIPAAm and the pH-sensitivity of PDMAEMA. A fluorescence probe study showed the pH-dependent low CMCs (7.5 to 11.2 mg/L) of the micelles, confirming the formation of stable micelles. Morphological investigations showed that the blank and drug-loaded micelles both had spherical and uniform shapes. The sizes of the blank and drug-loaded nanoparticles were between 80 and 120 nm, depending on the given pH. The LCSTs of the star copolymer were determined to be 32 °C, 36.6 °C and 39.5 °C, corresponding to pH 5, pH 7.4 and pH 9, respectively, demonstrating a pH-dependent thermo-response. As a drug delivery, the micellar nanoparticles showed the dual-responsive release profiles in vitro, which were confirmed by the drug release studies. The obtained results showed the thermo-triggered accelerated release at pH 7.4, and the pH-triggered accelerated release at 37 °C, indicating the micelles nanoparticles would be a promising site-specific drug delivery for enhancing the accumulation of drug in targeting pathological areas.

Graphical abstractThe self-assembly of the star copolymer and the structural changes in responsive to temperature and pH.Figure optionsDownload full-size imageDownload as PowerPoint slide