Solvent exchange methods for protein microencapsulation

描述（由申请人提供）：蛋白质药物的微胶囊化一直是开发长期递送制剂的首选方法。目前的微胶囊化方法，特别是溶剂萃取和溶剂蒸发方法，最初并不是为蛋白质药物的微胶囊化而开发的，因此它们在蛋白质微胶囊化中存在许多困难。传统的微胶囊化方法只能对部分蛋白质药物进行微胶囊化，本课题的目的是在近年来发现的“溶剂交换法”的基础上，开发新的微胶囊化技术。单个的含水蛋白质微滴用可生物降解的聚（乳酸-共-乙醇酸）（PLGA），使用喷墨技术在几分之一秒内形成真正的微胶囊。由于微囊化的时间非常短，大多数蛋白质药物不与PLGA和溶剂相互作用。在该项目中要测试的假设是，在水性蛋白质微滴上形成PLGA微胶囊取决于亲水性溶剂在水性表面上的铺展系数和溶剂的水溶性。本项目的具体目标是：（1）优化溶剂交换/喷墨技术的微胶囊化工艺;（2）寻找形成PLGA微胶囊的最佳可加工PLGA/溶剂体系;（3）寻找形成稳定微胶囊和保存蛋白质药物的水性微滴的最佳理化性质;（4）寻找形成稳定微胶囊的水性微滴的最佳理化性质。（4）制备载有蛋白质药物如人生长激素和促红细胞生成素的微胶囊，并检查所载药物的稳定性、它们的释放动力学和它们的长期稳定性;（5）研究蛋白质药物微囊化后的生物活性，为蛋白质药物微囊化提供一种新的方法。由于溶剂交换法操作简单，有望开辟多种性质蛋白质药物微胶囊化的新途径。

DESCRIPTION (provided by applicant): Microencapsulation of protein drugs has been the method of choice for developing long-term delivery formulations. The current methods of microencapsulation, especially solvent extraction and solvent evaporation methods, were not initially developed for microencapsulation of protein drugs, and for this reason they present a number of difficulties in protein microencapsulation. Only a selected number of protein drugs have been microencapsulated using the conventional methods.The objective of this project is to develop new microencapsulation technologies based on the "solvent exchange method" that we recently found. In the solvent exchange method, individual aqueous protein microdroplets are coated with biodegradable poly(lactic-co-glycolic acid) (PLGA) to form true microcapsules in a fraction of a second using the ink-jet technology. Because of the extremely short time period for microencapsulation, most protein drugs do not interact with PLGA and solvent. The hypothesis to be tested in this project is that formation of PLGA microcapsules on aqueous protein microdroplets depends on the spreading coefficient of a hydrophilic solvent on an aqueous surface and the water-solubility of the solvent. The specific aims of this project are: (1) to optimize the microencapsulation process using the solvent exchange/ink-jet technology; (2) to find the best processable PLGA/solvent systems for forming PLGA microcapsules; (3) to find the optimum physicochemical properties of aqueous microdroplets for formation of stable microcapsules and preservation of protein drugs; (4) to prepare microcapsules loaded with protein drugs, such as human growth hormone and erythropoietin, and examine the stability of the loaded drugs, their release kinetics, and their long-term stability; and (5) to examine the bioactivity of the protein drugs after release from microcapsules.The significance of this project is that a new microencapsulation method that is specifically designed for protein drugs will be developed. Because of the simplicity of the solvent exchange method, it is expected to open a new avenue of microencapsulation of protein drugs with various properties.