Thermosensitive PNIPAM semi-hollow spheres for controlled drug release

Thermosensitive poly(N-isopropylacrylamide) (PNIPAM) semi-hollow spheres consisting of low density cores, dense shells and separated cavities between cores and shells were prepared via two-step precipitation polymerization. The self-cross-linked poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-co-PMAA) gels with low solid density were prepared in the first precipitation polymerization and served as the templates on which dense PNIPAM shells cross-linked by N,N'-methylenebis(acrylamide) (BMA) were formed in the second precipitation polymerization. The shell thickness of the semi-hollow spheres could be controlled via adjusting the feeding core/shell mass ratios. The carboxylic groups on the core were conjugated with doxorubicin (DOX) via disulfide bonds which could be degraded by the reduction of glutathione (GSH). The release of DOX from the cores could be controlled by temperature and shell thickness with the disulfide bonds degraded by GSH. The cell viability assay indicated that the semi-hollow particles conjugated with DOX by disulfide bonds showed remarkable toxicity to Hela cells, and the toxicity was related to the shell thickness of the particles.