Formation of cycloextrin - drug inclusion complexes and scaffolds with the aid of supercritical fluids

借助超临界流体形成环外精-药物包合物和支架

• 批准号: 0929978
• 负责人: Erdogan Kiran
• 金额: $ 30.59万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0929978&HistoricalAwards=false
• 关键词: Formation; cycloextrin; drug; inclusion; complexes

0929978KiranThis is a research program on exploration of novel methodologies that aim at using supercritical fluids to form drug inclusion complexes with cyclodextrins, as well as forming polymer matrices or scaffolds that are embedded with drug-cyclodextrin complexes. Supercritical fluids are tunable fluids that can reduce or eliminate the use of organic solvents in synthesis, purification, and post-processing of biopolymers and drugs to generate particles, membranes or scaffolds that can be used in drug delivery or other medical devices. For drug delivery, particle size, shape, morphology and crystal form of the drug molecules are very important as they influence the rate of dissolution and the release characteristics of drugs. For scaffolds, porosity along with built-in drug-release features that incorporate anti-inflammatory drugs and/ or growth factors are important factors that ensure transport of nutrients, promotion of cell proliferation, and prevention of infections during organ regeneration. Cyclodextrins have hydrophobic internal cavities in which drug molecules can be incorporated as guest molecules. A unique aspect of this research is the exploration of development of novel drug-cyclodextrin complexes using polymeric forms of cyclodextrins, such as polymers with pendant cyclodextrin groups, which can be formed and directly transformed into porous scaffolds in supercritical fluid media. Formation of drug-cyclodextrin inclusion complexes within a biodegradable polymer matrix such as poly(å-caprolactone) is another novel aspect that aims at generation of tissue engineering scaffolds with a built-in and/or improved drug delivery feature. Dual drug delivery systems that combine drug-cyclodextrin matrices along with a growth factor embedded in biodegradable polymer matrices are being considered to generate novel scaffolds that incorporate in-situ drugs to minimize inflammation and in-situ growth factors that are critical in promoting organ regeneration.The research involves fundamental studies on miscibility and phase separation in multicomponent systems involving small (drug) and large (polymeric) molecules and supercritical fluid mixtures (carbon dioxide + cosolvent) to understand the overall thermodynamics, and the nano-scale dynamics of guest-host interactions involving drug molecules, cyclic compounds and polymers with cavities that can form inclusion complexes. Studies are directed to understanding the consequences of processing in supercritical fluid media in terms of morphology, crystallinity, and polymorphism as well as documentation of drug release dynamics from such multi-component matrices.The research program brings together the expertise of the PI in supercritical fluids and polymers with the expertise of the co-PI in natural polymer-based drug release and cellular engineering systems. The interdisciplinary nature of the program is expected to have a broad impact in a wide range of other application areas from polymers to sensors, and create broad educational opportunities to graduate and undergraduate students with different diversity, gender and backgrounds.

0929978Kiran这是一个探索新方法的研究计划，旨在使用超临界流体与环糊精形成药物包合物，以及形成嵌入药物-环糊精复合物的聚合物基质或支架。超临界流体是一种可调流体，可以在生物聚合物和药物的合成、纯化和后处理过程中减少或消除有机溶剂的使用，以生成可用于药物输送或其他医疗设备的颗粒、膜或支架。药物分子的颗粒大小、形状、形态和晶型直接影响药物的溶出速度和药物的释放特性，对药物的缓释具有重要意义。对于支架来说，孔隙率以及内置的药物释放功能(包括抗炎药和/或生长因子)是确保营养物质运输、促进细胞增殖和防止器官再生期间感染的重要因素。环糊精具有疏水的内腔，药物分子可以作为客体分子并入其中。这项研究的一个独特方面是探索利用环糊精的聚合物形式开发新型药物-环糊精复合体，例如带有侧链环糊精基团的聚合物，这些聚合物可以在超临界流体介质中形成并直接转化为多孔支架。在聚己内酯等可生物降解的聚合物基质中形成药物-环糊精包合物是旨在生成具有内置和/或改进的药物输送特征的组织工程支架的另一个新颖方面。将药物-环糊精基质和嵌入在可生物降解的聚合物基质中的生长因子结合在一起的双重给药系统正被考虑用来生成新型支架，这种支架结合了原位药物以最大限度地减少炎症和原位生长因子，而原位生长因子是促进器官再生的关键因素。研究涉及多组分体系的基础研究，包括小(药物)和大(聚合物)分子以及超临界流体混合物(二氧化碳+助溶剂)，以了解整体热力学，以及包括药物分子、环状化合物和具有可形成包合物的空穴的聚合物在内的客体相互作用的纳米尺度动力学。研究旨在了解在超临界流体介质中加工对形态、结晶度和多晶性的影响，以及从这种多组分基质中记录药物释放动力学。研究计划将超临界流体和聚合物中等电点的专业知识与天然聚合物药物释放和细胞工程系统中的共等电点的专业知识结合在一起。该项目的跨学科性质预计将在从聚合物到传感器的广泛其他应用领域产生广泛影响，并为不同多样性、性别和背景的研究生和本科生创造广泛的教育机会。