第4章_纳米药物载体20100504.pptVIP

4.3.4 纳米载体的修饰与改性 一般来说，由于普通纳米粒易被单核细胞吞噬系统、网状内皮系统中的巨噬细胞作为异物识别和吞噬，从而在体内的半衰期较短。为了减少或避免载体输送系统纳米粒在体内对吞噬细胞的趋向性，增加纳米粒与所在药物对非RES器官的分布及延长其在体内的循环时间，因此，长循环和靶向纳米载体系统是近年来的研究热点。 实现纳米粒长循环和靶向性的途径主要是通过纳米粒的表面修饰。 4.3.4 纳米载体的修饰与改性 对纳米粒进行表面修饰可以改变其表面性质，如电荷、亲水性等。 纳米粒表面亲脂性越大，则对其调理蛋白的吸附结合力越强——增加亲水性 纳米粒的表面电荷影响纳米粒与体内物质如调理素等的静电作用力 负电荷表面往往使纳米粒相对于正电荷或中性表面在体内更易被清除，而中性的表面最适合用于延长纳米粒在体内的循环时间。 非离子型表面活性剂修饰 4.3.4 纳米载体的修饰与改性 表面修饰用材料包括以下三类： PEG、PEO、Poloxamer等聚合物 壳聚糖、环糊精、肝素等多糖 亲水性延长在体内的循环时间和减少巨噬细胞的捕获 两亲性环糊精可增加药物包封率和载药量 阴离子多糖类聚合物肝素可作为亲水性部分与PMMA形成两亲性共聚物纳米粒，肝素的抗凝活性作用可以阻止血液成分对纳米粒的黏附以及对抗血浆蛋白质对药物的竞争而延长循环时间。 聚山梨酯、Tween-80等表面活性剂 4. 4 纳米药物载体的应用 Polymer-P/P Drug Complexes Covalent attachment of P/P Drugs to polymer chains via specific linkers. The micelles have a solid-like inner core, which serves as a potent nanocontainer of hydrophobic compounds for solubilization of chemotherapeutics, including docetaxel (DOC，多烯紫杉醇), paclitaxel (PTX，太平洋紫杉醇) , camptothecin(喜树碱), and dequalinium (DQA, 地喹氯铵). Lower critical solution temperature (LCST) polymers, such as poly (N-isopropylacrylamide) (PNIPAAm) with a cloud point around 32?C or some other poly (N-alkylacrylamide) compounds, were investigated as components of temperature-responsive copolymer micelles. The micelles exhibited rapid and temperature responsive drug release in cancer cells, which was caused by the destruction of the hydrophobic-hydrophilic balance with the increase of temperature. Licciardi et al. synthesized novel folic acid- (FA-) functionalized diblock copolymer micelles for target delivery of antitumor drugs. The micelles could be directly targeted delivery via folic acid and rapidly release of drug could be triggered by lowering the solution pH to 5. This strategy combined the targeted delivery of therapeutics and pH-controlled drug release together, providing a tumor-selective nanocarrier for the efficient delivery of anticancer drugs. Targeted Paclitaxel by Conjugation to Iron Oxide and Gold Nanoparticles Cyclodextrin conjugated magnetic colloidal