Configurational Biomimetic Imprinting Methods for Advanced Drug Delivery

德克萨斯大学奥斯汀分校的“构型仿生印迹方法用于高级药物输送”工程纳米生物材料通过控制识别和特异性是协调和复制复杂生物和生理过程的第一步。构型仿生印迹（CBIP）和纳米印迹技术是基于感兴趣的生物化合物创建立体特异性三维结合腔的技术，可生产用于智能药物传递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传递和识别生物重要分子。与生物网络相比，大分子网络将具有精确的化学结构，具有增强的机械、热学和识别特性。新型仿生分子印迹凝胶和分子印迹释放系统的合成和表征是本提案的一个重要重点。在聚合物设计中特别重要的是网络形态，它在交联密度（微孔和大孔区域）的空间变化。重点还放在单体链的柔韧性和大小、单体官能团的数量和化学性质以及官能团对产生空间定义的识别位点所需的特定识别事件的化学反应性的基础研究上。科学原理是基于这样的假设：通过适当调整凝胶功能和模板之间的非共价相互作用，例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，有效设计的印迹聚合物网络将具有优越的结合特性和在水环境中的定向识别。初步实验成功的印迹d -葡萄糖水溶液识别提供了令人鼓舞的结果在实验室。光谱、荧光和共聚焦显微镜分析将导致聚合物设计的有效优化。通过调整聚合物凝胶的结构组成，可以在聚合物凝胶中创建有效的识别位点。智力优势：这项研究将会提高我们在纳米器件领域的知识，这些纳米器件可以识别不需要的化学物质。这项工作对于开发和理解分子印迹聚合物网络的功能具有重要意义，可以用于各种高科技应用。从基本的角度来看，这项工作将为生物和化学实体存在下的扩散机制和反应提供重要的新理解。更广泛的影响：对该领域特别感兴趣的发展预计将是广泛而深远的，例如智能分析物调节药物递送，不良生物制剂的识别，纳米尺度的模式和蛋白质的识别，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，P.I.还在同一领域建立了一个本科生研究项目，每年吸引5-6名大三或大四的学生进行这些项目的研究。

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.