CONTROLLED RELEASE OF MACROMOLECULES

大分子的受控释放

• 批准号: 3274090
• 负责人: ROBERT Samuel LANGER
• 金额: $ 21.92万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3274090
• 关键词: DNA; active immunization; alkenes; artificial endocrine pancreas; biomaterial development /preparation; biomaterial interface interaction; chemical synthesis; clinical biomedical equipment; computer simulation; drug delivery systems; drug vehicle; enzyme therapy; macromolecule; magnetic field; mathematical model; model design /development; peptide hormone; pharmacokinetics; physical property; polymers; polyvinyls; scanning electron microscopy; slow release drug; spectrometry; tissue /cell culture; ultrasound

The area of controlled release delivery systems has been a field of increasing interest in the past decade. However, relatively little attention has been focused on the development of such systems for macromolecular (M.W. greater than 1000) drugs such as polypeptides. Several years ago, we were able to develop the first such biocompatible polymeric systems for delivering these large molecular weight drugs. The principal findings of our work during the current period include 1) using microstructural analysis and kinetic modeling to show that release is diffusion controlled 2) showing little to no fibrous encapsulation occurs even after seven months in vivo, 3) showing that release rates in vitro and in vivo are the same, 4) developing experimental methods to produce systems that release macromolecules at zero order rates for several months, 5) using these systems to prevent calcification of heart valves and diabetes in animal models, 6) synthesizing a new class of surface erosion controlled bioerodible polymers-polyanhydrides, 7) characterizing critical release parameters from magnetically controlled systems. This grant renewal proposal will address three significant areas which are either important extensions of work initiated in the previous grant proposal, or new concepts which we feel will be significant in the future of controlled release systems for large or small molecules. The following are the specific aims of the present proposal: 1) non-erodible systems - to develop models, microstructural analysis techniques and computer simulations capable of predicting the kinetics of release of macromolecules; 2) bioerodible systems - to engineer a class of biocompatible polymers with controllable bioerosion rates and to characterize the release-related properties of these polymers; 3) magnetically controlled systems - to better understand the factors controlling modulation, and to initate the development of predictive models.

控释递送系统领域已成为一个领域 过去十年中人们的兴趣日益浓厚。 但相对较少 人们的注意力集中在此类系统的开发上 大分子（分子量大于 1000）药物，例如多肽。 几年前，我们能够开发出第一个这样的生物相容性 用于输送这些大分子量药物的聚合物系统。 这 我们当前阶段工作的主要发现包括 1) 使用 微观结构分析和动力学模型表明释放是 扩散控制 2) 显示很少或没有发生纤维包封 即使在体内七个月后，3）显示体外和 体内相同，4）开发实验方法来生产系统 连续几个月以零订单率释放大分子，5) 使用这些系统来预防心脏瓣膜钙化和糖尿病 在动物模型中，6）合成一类新型的表面侵蚀控制 可生物侵蚀的聚合物-聚酸酐，7) 表征临界释放 来自磁控系统的参数。 本次补助金续展 提案将涉及三个重要领域，这些领域要么重要 先前拨款提案中启动的工作的扩展，或新的 我们认为这些概念在受控的未来将具有重要意义 大分子或小分子的释放系统。 以下是 本提案的具体目标： 1) 不可侵蚀系统 - 开发 模型、微观结构分析技术和计算机模拟 能够预测大分子释放的动力学； 2） 生物可蚀系统 - 设计一类生物相容性聚合物 可控的生物侵蚀速率并表征与释放相关的 这些聚合物的特性； 3）磁控系统——以 更好地理解控制调制的因素，并启动 预测模型的开发。