A stimulus-responsive magnetic nanoparticle drug carrier: Magnetite encapsulated by chitosan-grafted-copolymer

We describe a magnetic nanoparticle drug carrier for controlled drug release that responds to the change in external temperature or pH, with characteristics of longer circulation time and reduced side effects. The novel nanocarrier is characterized by a functionalized magnetite (Fe3O4) core that is conjugated with drug via acid-labile hydrazone-bond and encapsulated by the thermosensitive smart polymer, chitosan-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) [chitosan-g-poly(NIPAAm-co-DMAAm)]. The chitosan-g-poly(NIPAAm-co-DMAAm) smart polymer exhibits a lower critical solution temperature (LCST) of ∼38 °C, signifying phase transition behavior of the smart polymer and enabling its use for triggering on–off mechanisms. The drug release response was appreciably low at a temperature less than the LCST as compared with a temperature above the LCST. In each case, there was an initial rapid drug release, followed by a controlled released in the second stage, especially in a mild acidic buffer solution of pH 5.3. We believe that the drug release occurs via a collapse of the encapsulated thermosensitive polymer and cleavage of the acid-labile hydrazone linkage.