Thermo- and pH-sensitive ionic-crosslinked hollow spheres from chitosan-based graft copolymer for 5-fluorouracil release.

Thermo- and pH-sensitive ionic-crosslinked hollow spheres from self-assembly of chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAM) for controlled release of 5-fluorouracil were studied. CS-g-PNIPAM aggregated into core-shell micelles with collapsed PNIPAM as the core and CS as the shell at the temperature above LCST. Ionic crosslinking reagent sodium tripolyphosphate (TPP) was used to crosslink the shell to form hollow spheres after cooling to room temperature. The size of hollow spheres was manipulated by changing pH or temperature of the environment. The CS-g-PNIPAM hollow spheres with plenty of inner cavities showed high loading capacity for 5-fluorouracil due to the polymer-drug interactions. Release of 5-fluorouracil from nanoparticles was accelerated at the temperature above LCST ascribed to the destruction of polymer-drug interactions and the decrease of particles size. Changing pH or ionic strength deformed the structure hollow spheres, which led to the increase of drug release. These hollow nanoparticles with environmentally sensitive properties are expected to be utilized in the field of intelligent drug delivery.