Yuan Q, Venkatasubramanian R, Hein S, Misra R D K
Biomaterials and Biomedical Engineering Focused Research Group, Center for Structural and Functional Materials, University of Louisiana at Lafayette, Lafayette, LA 70504-4130, USA.
Acta Biomater. 2008 Jul;4(4):1024-37. doi: 10.1016/j.actbio.2008.02.002. Epub 2008 Feb 15.
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 (Fe(3)O(4)) 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 approximately 38 degrees 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.
我们描述了一种用于药物控释的磁性纳米颗粒药物载体，它能响应外部温度或pH值的变化，具有循环时间更长和副作用更小的特点。这种新型纳米载体的特征在于功能化的磁铁矿（Fe(3)O(4)）核心，该核心通过酸不稳定的腙键与药物共轭，并被热敏智能聚合物壳聚糖-g-聚（N-异丙基丙烯酰胺-co-N,N-二甲基丙烯酰胺）[壳聚糖-g-聚（NIPAAm-co-DMAAm）]包裹。壳聚糖-g-聚（NIPAAm-co-DMAAm）智能聚合物表现出约38摄氏度的较低临界溶液温度（LCST），这表明了智能聚合物的相变行为，并使其能够用于触发开关机制。与高于LCST的温度相比，在低于LCST的温度下药物释放响应明显较低。在每种情况下，都有一个初始的快速药物释放，随后在第二阶段进行控释，特别是在pH 5.3的温和酸性缓冲溶液中。我们认为药物释放是通过包裹的热敏聚合物的塌陷和酸不稳定腙键的断裂而发生的。
