Microenvironment-Controlled Encapsulation (MICE) Process

描述(由申请人提供)： 微胶囊是开发长期给药的肠外制剂的首选方法。然而，目前的微胶囊化方法在蛋白质药物的微胶囊化方面存在许多困难。出于这个原因，使用传统方法只报告了有限数量的成功。 本项目的目的是开发一种新的微胶囊系统，利用成熟的流式细胞仪技术来生产均一的聚合物微胶囊，这种微胶囊可以控制药物的释放速度，同时在产品的整个生命周期中保持所包裹的药物的稳定性。在这项新技术中，我们称之为微环境控制封装(MICE)过程，通过使用流式细胞仪对组成液体进行流体动力学聚焦来生成高度均匀的单核微胶囊。该项目基于这样的假设：(A)通过单独加工成分材料，可以最大限度地减少对被包裹药物的机械和化学应力；(B)通过精确控制形成微胶囊的特定环境，可以获得均匀的微胶囊。该项目的具体目标是：(1)了解和优化小鼠的过程；(2)获得对微环境的控制；(3)表征微囊的物理性质和包裹的蛋白质的完整性；(4)提供能够控制体外药物释放的微胶囊系统。 MICE过程的意义在于，通过利用现有的流式细胞仪技术，可以在对包裹的药物施加最小压力的情况下，高频地生产尺寸和几何形状高度均一的微囊。MICE过程将促进各种用传统方法难以配制的蛋白质药物以及小分子药物的微胶囊。

DESCRIPTION (provided by applicant): Microencapsulation is the method of choice for developing parenteral formulations for long-term drug delivery. However, current methods of microencapsulation present a number of difficulties in microencapsulation of protein drugs. For this reason, only a limited number of successes have been reported using the conventional methods. The objective of this project is to develop a new microencapsulation system utilizing well-established flow cytometry technology to produce homogeneous polymeric microcapsules that can control the drug release rate while maintaining the stability of the encapsulated drug throughout the lifetime of the product. In this new technique, which we call the Microenvironment-Controlled Encapsulation (MICE) process, highly homogeneous mononuclear microcapsules are generated by hydrodynamically focusing the component liquids using a flow cytometer. This project is based on the hypotheses that (a) the mechanical and chemical stresses on the encapsulated drugs can be minimized by separately processing the component materials; and (b) homogeneous microcapsules can be obtained by precise control of specific environments in which the microcapsules form. The specific aims of this project are: (1) to understand and optimize the MICE process; (2) to gain control over the microenvironment; (3) to characterize the physical properties of the microcapsules and the integrity of encapsulated protein; and (4) to provide a microcapsule system that is capable of controlling the in vitro drug release rate. The significance of the MICE process is that microcapsules, which are highly homogeneous in size and geometry, can be produced at a high frequency by taking advantage of existing flow cytometry technology with minimal stresses to the encapsulated drugs. The MICE process will facilitate microencapsulation of a variety of protein drugs that have been difficult to formulate with the conventional methods, as well as small molecular weight drugs.