Configurational Biomimetic Imprinting Methods for Advanced Drug Delivery

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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.