Configurational Biomimetic Imprinting Methods for Advanced Drug Delivery

用于先进药物输送的构型仿生印迹方法

• 批准号: 0329317
• 负责人: Nicholas Peppas
• 金额: $ 19万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-11-01 至 2006-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0329317&HistoricalAwards=false
• 关键词: Configurational; Biomimetic; Imprinting; Methods; Advanced

Nikolaos A. PeppasUniversity of Texas - Austin "Configurational Biomimetic Imprinting Methods for Advanced Drug Delivery"Engineering nano-biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. Configurational biomimetic imprinting (CBIP) and nanoimprinting techniques, which create stereo-specific three-dimensional binding cavities based on a biological compound of interest, produce biomimetic materials for intelligent drug delivery and drug targeting applications. Of particular interest are intelligent analyte-modulated drug delivery and recognition of biologically significant molecules. Macromolecular networks will be developed with precise chemical architecture that possess enhanced mechanical, thermal, and recognition properties compared to their biological counterparts. The synthesis and characterization of novel biomimetic molecularly imprinted gels and molecularly imprinted release systems is a significant focus of this proposal. Of particular importance in polymer design is the network morphology, which spatially varies in crosslinking density (microporous and macroporous regions). Emphasis is also placed on fundamental studies regarding the monomer chain flexibility and size, the number and chemical nature of monomer functional groups, and the chemical reactivity of the functional groups on the specific recognition event needed to produce a spatially defined recognition site. Scientific rationale is based on the hypothesis that effectively designed imprinted polymer networks will have superior binding properties and directed recognition in aqueous environments by properly tuning non-covalent interactions between the gel functionality and template such as increasing or decreasing macromolecular chain hydrophobicity, including strong hydrogen bond donors and acceptors, or including strong ionic directed recognition sites. Preliminary experimental success imprinting D-glucose for aqueous recognition has provided encouraging results within the laboratory. Spectroscopic and fluorescent and confocal microscopy analysis will lead to efficient optimization of polymer design. By tailoring the polymer gel structure composition, effective recognition sites for can be created in polymer gels. Intellectual Merit: The proposed research will advance our knowledge in the field of nanodevices that can recognize undesirable chemicals. This work is of major importance in the development and understanding of the function of molecularly imprinted polymer networks, which can be used in a variety of high technology applications. From a fundamental point of view, this work will provide significant new understanding of how diffusional mechanisms and reactions in the presence of biological and chemical entities. Broader Impact: Developments of particular interest to the field are expected to be wide and far reaching, such as intelligent analyte-modulated drug delivery, recognition of undesirable biologicals, nano-scale patterning and recognition of proteins, site-specific interaction with tissues, etc. The students will be trained and educated in all aspects of the field of molecular recognition. In addition, the P.I. has established an undergraduate research program in the same field which attracts 5-6 juniors or seniors per year who do research on these projects.

尼古拉斯·A PeppasUniversity of Texas - Austin“先进药物递送的仿生学印迹方法”通过控制识别和特异性来工程化纳米生物材料是协调和复制复杂生物和生理过程的第一步。 基于感兴趣的生物化合物产生立体特异性三维结合腔的仿生印迹（CBIP）和纳米印迹技术产生用于智能药物递送和药物靶向应用的仿生材料。特别感兴趣的是智能分析物调节的药物递送和生物学上重要分子的识别。大分子网络将开发具有精确的化学结构，具有增强的机械，热，和识别性能相比，其生物对应物。新型仿生分子印迹凝胶和分子印迹释放系统的合成与表征是本研究的重点。在聚合物设计中特别重要的是网络形态，其交联密度在空间上变化（微孔和大孔区域）。 重点也放在关于单体链的灵活性和大小的基础研究，单体官能团的数量和化学性质，和化学反应性的官能团上的特定识别事件需要产生一个空间定义的识别位点。 科学原理是基于这样的假设，即有效设计的印迹聚合物网络将具有上级结合特性，并通过适当调节凝胶功能和模板之间的非共价相互作用，如增加或减少大分子链疏水性，包括强氢键供体和受体，或包括强离子定向识别位点，在水性环境中定向识别。初步实验成功印迹D-葡萄糖水识别提供了令人鼓舞的结果在实验室内。 光谱和荧光和共聚焦显微镜分析将导致聚合物设计的有效优化。通过定制聚合物凝胶结构组成，可以在聚合物凝胶中产生有效的识别位点。智力优势：拟议的研究将推进我们在纳米器件领域的知识，可以识别不受欢迎的化学品。这项工作是非常重要的分子印迹聚合物网络，可用于各种高科技应用的功能的发展和理解。从基本的角度来看，这项工作将提供重要的新的理解如何扩散机制和反应中存在的生物和化学实体。更广泛的影响：该领域特别感兴趣的发展预计将是广泛和深远的，如智能分析物调制的药物输送，识别不需要的生物制剂，纳米尺度的图案化和蛋白质的识别，与组织的位点特异性相互作用等，学生将在分子识别领域的各个方面接受培训和教育。此外，PI。在同一领域建立了一个本科研究计划，每年吸引5-6名大三或大四学生从事这些项目的研究。