Zhang J, Misra R D K
Biomaterials Group, Center for Structural and Functional Material and Department of Chemical Engineering, University of Louisiana at Lafayette, P.O. Box 44130, Lafayette, LA 70504-4130, USA.
Acta Biomater. 2007 Nov;3(6):838-50. doi: 10.1016/j.actbio.2007.05.011. Epub 2007 Jun 29.
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 (Fe(3)O(4)) 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 (HSCH(2)CH(2)CONHNH(2)) 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 HSCH(2)CH(2)CONHNH(2) with the carbonyl group of doxorubicin. The dextran-g-poly(NIPAAm-co-DMAAm) smart polymer exhibits a lower critical solution temperature (LCST) of approximately 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.
描述了一种新型磁性药物靶向载体，它由包裹有具有可控药物释放特性的智能聚合物的磁性纳米颗粒组成。该载体的特征在于功能化的磁铁矿（Fe(3)O(4)）和共轭治疗剂阿霉素，阿霉素被热敏聚合物葡聚糖-g-聚（N-异丙基丙烯酰胺-co-N，N-二甲基丙烯酰胺）[葡聚糖-g-聚（NIPAAm-co-DMAAm）]包裹。磁铁矿纳米颗粒的表面通过与3-巯基丙酸酰肼（HSCH(2)CH(2)CONHNH(2)）经由Fe-S共价键进行化学键合而功能化。抗癌治疗药物阿霉素通过酸不稳定的腙键连接到功能化磁性纳米颗粒的表面，该键由HSCH(2)CH(2)CONHNH(2)的酰肼基团与阿霉素的羰基反应形成。葡聚糖-g-聚（NIPAAm-co-DMAAm）智能聚合物表现出约38℃的较低临界溶液温度（LCST），这代表了一种相变行为。这种行为允许一种开-关触发机制。在低于LCST的实验温度下，药物释放非常低。然而，在高于LCST的温度下，最初会有快速的药物释放，随后在第二阶段进行可控释放，特别是在pH 5.3的轻度酸性缓冲溶液中。药物的释放被设想为通过包裹的热敏聚合物的塌陷和酸不稳定的腙键的断裂而发生。所提出的载体适用于具有更长循环时间、减少副作用以及响应外部温度变化而实现可控药物释放的磁性靶向给药系统。
