胶束表面亲疏水性与其体内分布关系的研究

项目名称： 胶束表面亲疏水性与其体内分布关系的研究

项目编号： No.51203189

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 刘金剑

作者单位： 中国医学科学院

项目金额： 25万元

中文摘要： 高分子材料可以作为药物载体起到很好的药物缓控释及提高药物利用度的作用，但目前纳米药物载体普遍存在着在肝和脾中蓄积的问题，造成血液中载体和药物浓度降低，以致无法达到理想的治疗效果。造成纳米载体在肝和脾中蓄积的原因较多，包括纳米载体的尺寸、组成成分、表面带电性质等，我们前期预实验研究发现载体的表面亲疏水性也是其中的一个重要因素，但到目前为止国内外还未见相关的系统研究报道。因此本项目拟通过嵌段共聚物自组装方法制备一系列具有表面亲疏水梯度性质的纳米复合胶束，经放射性核素碘[125]标记后考察不同组成的复合胶束在动物体内的分布情况，系统地研究胶束的表面亲疏水性质对其体内分布的影响，从而将获得在肝、脾等脏器截留量小而在血液循环分布较多的聚合物纳米胶束，为设计和制备体内血液循环时间长、利用率高的纳米药物载体提供理论依据和实验基础。

中文关键词： 复合胶束；亲疏水性；药物载体；同位素示踪；组织分布

英文摘要： Ploymeric materials can be used as drug carriers to control drug release and improve drug bioavailability, but most of nano-drug carriers are often accumulated in liver and spleen, which results in low concentrations of carriers and drugs in blood and poor therapeutic effect. There are many reasons for the accumulation of nano-drug carriers in liver and spleen, including the sizes of nano carriers, composition, charge properties of surface and others. In our preliminary study, we found that the hydrophilicity and hydrophobicity of nano carriers are also important influencing factors, but few systematic research has been reported so far. In this project, we want to prepare a series of nano-polymeric micelles with hydrophilic/hydrophobic gradient on the surface by block copolymer self-assembly and perform in vivo study on the biodistribution of the series of polymeric micelles by labeling with radionuclide iodine-125. By systematic study on the effect of micelle's surface hydrophilicity and hydrophobicity on their biodistribution, we expect to gain the polymeric nano-carriers which have a lower accumulation in liver and spleen but higher in blood circulation, and to provide a theoretical foundation for design and preparation of nano-drug carriers with longer blood circulation and higher bioavailability.

英文关键词： polymeric micelle；hydrophilicity and hydrophobicity；drug carriers；isotopic tracing；biodistribution