Monodisperse temperature-responsive hollow polymer microspheres: Synthesis, characterization and biological application

Temperature-responsive hollow poly(N-isopropylacrylamide) (PNIPAAm) microspheres were prepared by a two-stage distillation precipitation polymerization to afford a core–shell microspheres with subsequent removal of poly(methacrylic acid) (PMAA) core. PMAA@PNIPAAm core–shell microspheres were synthesized by the second-stage polymerization of NIPAAm in the presence of PMAA as core with N,N′-methylenebisacrylamide as crosslinker in acetonitrile, in which the hydrogen-bonding interaction between the carboxylic acid group of PMAA core and the amide group of NIPAAm as well as MBAAm played a key role to form the core–shell microspheres. The hollow PNIPAAm microspheres with different thicknesses, which were controlled by the monomer loading level and the crosslinking degree, were developed after the removal of PMAA core. The loading and controlled-release behavior of the drug on the hollow PNIPAAm microspheres was investigated with doxorubicin hydrochloride. The core–shell and hollow microspheres were characterized with transmission electron microscopy, scanning electron microscopy, dynamic light scattering, static light scattering, X-ray photoelectron spectroscopy, elemental analysis, and FT-IR spectra.