项目名称： 基于微流控芯片技术制备多功能靶向siRNA脂质纳米粒及其合成机制的研究

项目编号： No.81502999

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 滕乐生

作者单位： 吉林大学

项目金额： 17.9万元

中文摘要： 本项目采用倒W型等新型微流控芯片合成高效、靶向的寡核苷酸传输载体，并对微流控芯片合成载体的合成机制进行研究。微流控芯片技术是一种新型的药物载体制备技术，能够在微米级尺寸内精确控制和操作液体流动。同常规制备方法相比，微流控芯片技术混合方式为平流，所制备的纳米粒子的分散性、包封率、重现性好，且制备的电子致密核心结构更易被细胞吸收。然而，在应用中受制于芯片本身反应空间小，平流合成时两相间分子的扩散慢，制备效率很低；而且，微流控芯片合成电子致密核心结构的合成机制不清楚。本项目制备倒W型等新型微流控芯片以增加在平流状态下两相间的混合效率，提高制备效率及改善脂质纳米粒的物理、化学及药学性质；提出一种符合微流控合成载体实际情况的堆积参数理论，并验证其是否是微流控芯片合成的机理。本研究的顺利实施，将为靶向载体的制备提供新的思路及方法，具有理论意义和应用前景。

中文关键词： 微流控芯片；小干扰RNA；脂质纳米粒

英文摘要： In this project, a new types of microfluidic chips such as the inverted W-type, were developed to synthesize the efficient and targeted oligonucleotide-lipid nanoparticles. The synthesis mechanisms on the used microfluidic chips were thoroughly studied. Microfluidic chip technology is a novel preparation approach for drug delivery, which can precisely control and manipulate the flow of liquids in micron size. Compared with the conventional preparation methods, microfluidic chip technology (MFCT) can produce nanoparticles with excellent dispersion, encapsulation efficiency and reproducibility because of Laminar flow. Furthermore, the resultant nanoparticles via MFCT are almost the electron-dense core structure and more easily absorbed by the cells. However, due to the small reaction space in microfluidic chip, the advection diffusion of synthetic molecules between two phases is slow and the production efficiency is normally low. More importantly, the synthesis mechanism on the nanoparticles with high electron-dense core structure via MFCT is unclear. A series of the inverted W-typed microfluidic chips were designed and prepared in this project. The new microfluidic chips were used to increase the efficiency of mixing in the stratosphere state between the two phases. The production efficiency and the physical, chemical and pharmaceutical properties of lipid nanoparticles were significantly improved as well. In this project, a synthesis theory on microfluidic packing parameter control was presented to support the experimental data. The successful implementation of this project may provide new methods on the preparation of the targeted lipid nanoparticles, which has the important theoretical value and application prospects.

英文关键词： Microfluidic;siRNA;lipid nanoparticles