pH, temperature and reduction multi-responsive polymeric microspheres as drug delivery system for anti-tumor drug: Effect of middle hollow layer between pH and reduction dual-responsive cores and temperature sensitive shells

•pH, temperature and reduction multi-responsive polymeric microspheres were designed.•Effect of the middle hollow layer on their drug loading and drug release was investigated.•This understanding must be helpful on designing intelligent anti-tumor DDS.

Multi-responsive polymeric microspheres have attracted more and more interest as drug delivery system (DDS) for anti-tumor drugs because they could achieve “on-demand” drug release, triggered by the tumor micro-environment. Here the pH, temperature and reduction multi-stimuli responsive polymeric microspheres were fabricated via distillation-precipitation polymerization technique, with or without the middle hollow layer between their pH and reduction responsive poly(methacrylic acid) (PMAA) cores and temperature sensitive poly(N-isopropylacrylamide) (PNIPAM) shells. The effect of the hollow layer on their drug loading and drug release performance was investigated in detail. It was found that the PMAA/PNIPAM yolk/shell microspheres with hollow layer possessed a higher drug loading capacity, while the PMAA/PNIPAM core/shell microspheres without hollow layer exhibited a better controlled release behavior. This understanding must be helpful on designing intelligent anti-tumor DDS.

Graphical abstractDownload high-res image (132KB)Download full-size image