基于磁性葡聚糖纳米水凝胶的双功能药物载体的构建及其性能研究

设计和构建具有靶向及成像多功能的药物载体系统是目前药物控释领域的发展趋势，磁性葡聚糖纳米水凝胶作为载药材料具有优良的生物安全性、磁靶向性及磁共振成像功能，但目前对其制备方法及性能评价的研究报道较少。本项目拟以氧化铁纳米粒子为磁性组分，通过反相微乳液法构建磁性葡聚糖纳米水凝胶作为双功能药物载体材料：1）对交联反应条件、交联剂结构、构成微乳液的表面活性剂种类进行筛选，探索适用于制备葡聚糖纳米水凝胶的反相微乳液体系，制备形貌、粒径均匀可控的葡聚糖纳米水凝胶；2）将氧化铁纳米粒子通过原位生成及作为交联剂的方法引入葡聚糖纳米水凝胶的网络结构中，并与常用的物理掺杂方法进行对比，构建具有优良磁学性能的磁性复合纳米水凝胶；3）对该磁性葡聚糖纳米水凝胶作为双功能药物载体的体外载药及释放行为、磁共振成像效果进行初步研究。本项目的实施将获得一类基于磁性水凝胶微球的药物载体，并为其体外载药及成像性能提供理论依据。

Multifunctional drug delivery systerms (DDS) that incorporate therapeutic agents, molecular targeting and imaging capabilities into a single nanoplatform have gained considerable attention in recent years. As one of the most promising DDS, magnetic hydrogel nanoparticles based on natural polymer have shown significant potential owning to their excellent biocompatibility, magnetic targeting ability and fuctions as magnetic resonance imaging (MRI) contrast agent. In this project, we aim to develop a series of magnetic hydrogel nanoparticles based on dextran and superparamagnetic iron oxide nanoparticle, and their functions as drug carriers and MRI contrast agent will be evaluated. In order to prepare hydrogel nanoparticles, dextran will be chemically modified, and then crosslinked in an inverse miniemulsion system. Parameters which can dramatically influence the physical and chemical properties of the resulted hydrogel nanoparticles, including crosslinking degree, molecular structure of the crosslinker, surfactants, will be optimized. Furthermore, paramagnetic iron oxide nanocrystals will be introduced into the networks of hydrogel particles via three different methods: physical doping, in situ coprecipitation, and using modified iron oxide nanoparticle as crosslinker. We seek to detemine and delineate the physical and chemical properties of the novel magnetic hydrogel nanocomposite and develop a nanoplatform as drug carrier and MRI contrast agent. If successful, the proof-of-concept will lead to a promising dual-functional DDS for biomedical applications.