A Remarkable Impact of pH on the Thermo-Responsive Properties of Alginate-Based Composite Hydrogels Incorporating P2VP-PEO Micellar Nanoparticles.

A heterograft copolymer with an alginate backbone, hetero-grafted by polymer pendant chains displaying different lower critical solution temperatures (LCSTs), combined with a pH-responsive poly(2-vinyl pyridine)--poly(ethylene oxide) (P2VP--PEO) diblock copolymer forming micellar nanoparticles, was investigated in aqueous media at various pHs. Due to its thermo-responsive side chains, the copolymer forms hydrogels with a thermo-induced sol-gel transition, above a critical temperature, T (thermo-thickening). However, by lowering the pH of the medium in an acidic regime, a remarkable increase in the elasticity of the formulation was observed. This effect was more pronounced in low temperatures (below T), suggesting secondary physical crosslinking, which induces significant changes in the hydrogel thermo-responsiveness, transforming the sol-gel transition to soft gel-strong gel. Moreover, the onset of thermo-thickening shifted to lower temperatures followed by the broadening of the transition zone, implying intermolecular interactions between the uncharged alginate backbone with the PNIPAM side chains, likely through H-bonding. The shear-thinning behavior of the soft gel in low temperatures provides injectability, which allows potential applications for 3D printing. Furthermore, the heterograft copolymer/nanoparticles composite hydrogel, encapsulating a model hydrophobic drug in the hydrophobic cores of the nanoparticles, was evaluated as a pH-responsive drug delivery system. The presented tunable drug delivery system might be useful for biomedical potential applications.