超重力法可控制备自组装型智能纳米微胶囊机制及应用基础研究

Microcapsules can be used as drug carriers for drug delivery systems to achieve drug encapsulation and intelligently controllable release in order to improve the targeting efficiency, safety and effectiveness of drugs. This technology is one of the international cutting-edge research directions. In this project, we propose a new idea of "double high gravity " method for the efficiently controllable preparation of nano-sized colloidosomes, which is based on molecular chemical engineering. Here, a high gravity rotating packed bed (RPB) will be used to generate a highly strengthened micro-mixing environment. Firstly, small, tunable and pH-responsive latex particles, as capsule shell materials, will be prepared by high gravity emulsion polymerization method in an internal circulation RPB. Then the latex particles and oil phase solutions will be simultaneously introduced into an external circulation RPB for high gravity emulsification. After heating, centrifugation, washing and re-dispersing processes, the smart nano-sized colloidosomes can be created with controllable structure and high performance. This project focuses on the mechanism of controllable preparation of nano-sized colloidosomes. We will explore the mechanism and regulation of the enhanced emulsion polymerization and emulsification processes in the high gravity environment. In addition, the mechanism of drug encapsulation and intelligently controllable release in colloidosomes will be explored and revealed. The constitutive relationship of “preparation technology - morphological structures - application properties” will be constructed. The implementation of this project will provide a technical route and scientific basis for the efficient and controllable preparation of new nano-sized colloidosomes and the application of drug sustainable and controllable release.

微胶囊作为药物载体应用于药物传输系统，可实现对药物的包埋和智能化控释，进而提高药物的靶向利用率、安全性和有效性，是国际前沿研究方向。本项目基于分子化学工程原理，提出“双超重力”法高效可控制备自组装型纳米微胶囊的新思想，即利用超重力旋转填充床（RPB）内产生的极大强化的微观混合环境，首先在内循环RPB内，采用超重力乳液聚合制备小尺寸且可调的pH响应型囊壁材料，然后将囊壁材料和油相溶液同时导入外循环RPB内进行超重力乳化，再经加热、离心、洗涤、再分散，从而实现结构可控的高性能自组装型智能纳米微胶囊的创制。本项目重点研究自组装型纳米微胶囊可控制备机制，探究超重力环境下强化乳液聚合反应及乳化过程的作用机制和调控规律，探寻并揭示所得微胶囊的药物包埋和智能控释机理，构建“制备工艺－形态结构－应用性能”的本构关系。本项目的实施将为新型纳米微胶囊的高效可控制备和药物缓控释应用提供技术路线和科学基础。

药物载体材料作为药物传输系统中重要的组成部分，被广泛应用于医药行业。自组装型智能微胶囊作为一种新型药物载体，其结构和有效孔径会随着外界环境刺激的改变而发生变化，具有智能缓释和控释药物的特性，可提高药物的靶向利用率、安全性和有效性。现有制备自组装型微胶囊的方法由于受传统乳化过程分子混合速度的限制，较难获得尺寸均一且相对较小的微乳液，因此，会影响最终微胶囊产品的结构，尺寸及应用性能。本项目提出采用超重力乳液聚合法制备具有不同玻璃态转化温度及pH响应特性的聚合物颗粒水相悬浮液作为囊壁材料，并揭示了可控制备机制和调控规律。相比于传统釜式法，超重力法所制得的产品平均粒径更小，粒径分布更窄，且反应时间明显缩短。进一步利用超重力旋转填充床内产生的极大强化的微观混合环境，快速完成水相悬浮液在油相葵花籽油中的乳化过程，制得油包水型Pickering乳液，再经加热、离心、洗涤、再分散进而制备自组装型微胶囊。将其用于药物包埋及智能缓控释研究，创制出具有不同缓释性能及pH响应特性的微胶囊药物制剂。与乳化机所制备的微胶囊相比，超重力法所制备的微胶囊粒径相对更小，粒径分布更窄且产率更高。基于超重力法宏量制备微胶囊的研究结果，进一步拓展此类微胶囊的制备方法，采用喷雾干燥技术制备了具有不同缓释性能的自组装型微胶囊及磁响应型微胶囊。本项目已在Langmuir期刊发表论文1篇，Industrial & Engineering Chemistry Research期刊发表论文2篇，共发表SCI论文3篇；申请相关中国发明专利2件（均已授权）；培养博士研究生1名（在读），硕士研究生1名（已毕业，继续攻读博士学位）。