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给药配方的首选方法。目前的微胶囊化方法，尤其是溶剂萃取法和溶剂蒸发法，最初并不是为蛋白质药物的微胶囊化而开发的，因此它们给蛋白质微胶囊化带来了许多困难。使用常规方法进行微囊化的蛋白质药物只有少数。这个项目的目标是在我们最近发现的“溶剂交换法”的基础上开发新的微胶囊化技术。在溶剂交换法中，单个水性蛋白质微滴被生物可降解的聚乳酸-羟基乙酸（PLGA）包裹，使用喷墨技术在不到一秒的时间内形成真正的微胶囊。由于微囊化时间极短，大多数蛋白质药物不与PLGA和溶剂相互作用。本项目要验证的假设是，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表面的扩散系数和溶剂的水溶性。本课题的具体目标是：(1)利用溶剂交换/喷墨技术优化微胶囊化工艺；(2)寻找形成PLGA微胶囊的最佳可加工PLGA/溶剂体系；(3)为制备稳定的微胶囊和保存蛋白质药物寻找最佳的水微滴物理化学性质；(4)制备装载人生长激素、促红细胞生成素等蛋白类药物的微胶囊，并考察其稳定性、释放动力学和长期稳定性；(5)检测蛋白质药物微胶囊释放后的生物活性。本项目的意义在于开发出一种专门为蛋白质类药物设计的新型微胶囊化方法。由于溶剂交换法的简单性，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.