Magnetic drug-targeting carrier encapsulated with thermosensitive smart polymer: Core-shell nanoparticle carrier and drug release response

A novel magnetic drug-targeting carrier consisting of magnetic nanoparticles encapsulated with a smart polymer with characteristics of controlled drug release is described. The carrier is characterized by functionalized magnetite (Fe3O4) and conjugated therapeutic agent doxorubicin, which is encapsulated with the thermosensitive polymer, dextran-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) [dextran-g-poly(NIPAAm-co-DMAAm)]. The surface of magnetite nanoparticles was functionalized by chemical bonding with 3-mercaptopropionic acid hydrazide (HSCH2CH2CONHNH2) via Fe-S covalent bonds. The anticancer therapeutic drug, doxorubicin, was attached to the surface of the functionalized magnetic nanoparticles through an acid-labile hydrazone-bond, formed by the reaction of hydrazide group of HSCH2CH2CONHNH2 with the carbonyl group of doxorubicin. The dextran-g-poly(NIPAAm-co-DMAAm) smart polymer exhibits a lower critical solution temperature (LCST) of similar to 38 degrees C, which is representative of a phase transition behavior. This behavior allows for an on-off trigger mechanism. At an experimental temperature lower than LCST, the drug release was very low. However, at a temperature greater than LCST, there was an initially rapid drug release followed by a controlled released in the second stage, especially, in the mild acidic buffer solution of pH 5.3. The release of drug is envisaged to occur by the collapse of the encapsulated thermosensitive polymer and cleavage of the acid-labile hydrazone linkage. The proposed carrier is appropriately suitable for magnetic targeting drug delivery system with longer circulation time, reduced side effects and controlled drug release in response to the change in external temperature. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.