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

[0929978] kiran这是一个探索新方法的研究项目，旨在利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、纯化和后处理中减少或消除有机溶剂的使用，以产生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、形态和晶型对药物的释放速度和释放特性有重要影响。对于支架来说，孔隙度以及内置的抗炎药物和/或生长因子的药物释放特性是确保营养物质运输、促进细胞增殖和预防器官再生过程中感染的重要因素。环糊精具有疏水的内腔，其中药物分子可以作为客体分子掺入。本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-环糊精复合物，例如具有垂坠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。在可生物降解的聚合物基质（如聚<s:1> -己内酯）中形成药物-环糊精包合物是另一个新的方面，旨在产生具有内置和/或改进的药物传递特性的组织工程支架。将药物-环糊精基质与嵌入在可生物降解聚合物基质中的生长因子结合起来的双重药物传递系统被认为可以产生新的支架，这种支架可以结合原位药物来减少炎症和原位生长因子，而原位生长因子对促进器官再生至关重要。该研究包括对小分子（药物）和大分子（聚合物）以及超临界流体混合物（二氧化碳+助溶剂）的多组分体系的混相和相分离的基础研究，以了解整体热力学，以及涉及药物分子、环状化合物和具有可形成包合物的空腔的聚合物的主客相互作用的纳米尺度动力学。研究的目的是了解在超临界流体介质中处理的结果，包括形态、结晶度和多态性，以及从这种多组分基质中记录药物释放动力学。该研究项目将PI在超临界流体和聚合物方面的专业知识与co-PI在天然聚合物药物释放和细胞工程系统方面的专业知识结合在一起。该计划的跨学科性质预计将对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。

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.