Development of a new Imaging Platform for Pharmaceutical and Biomedical applicati

描述（由申请人提供）：在本项目中，Anasys Instruments首创的突破性纳米红外（IR）光谱新技术将被用于制药和生物系统。该技术有许多应用，如多晶筛选；亚细胞光谱学和药物-聚合物复合材料。在这项研究计划中，我们将重点展示纳米级红外平台的概念证明，以充分表征药物-聚合物系统的微观和纳米结构，普渡大学的Taylor教授是该领域的专家。该测量技术是基于原子力显微镜（AFM）探针与衰减全反射（ATR）棱镜接触，在吸收消失的中红外波后，检测样品的热膨胀的能力。利用该技术，既可以获得局部中红外光谱，也可以获得特定波长的图像。这项突破性的技术有潜力全面表征药物-聚合物体系的微观和纳米结构。因此，可以对系统的色散状态有深入的了解。这可以填补目前在理解制造和配方变量与药物-聚合物系统的最终产品性能之间的关系方面的空白。该项目旨在最大限度地提高该技术的空间（与成像过程相关的分辨率）和化学（基于后续成像数据分析处理的化学区分域的能力）分辨率。所选择的模型系统将由一组具有代表性的药物-聚合物复合材料组成。该模型聚合物将涵盖一系列聚合物类型，包括用于口服给药的聚合物（聚乙烯氧化物，纤维素基聚合物），可生物降解聚合物（聚乳酸，聚乳酸乙醇酸）和不可腐蚀的设备涂层聚合物（聚乙烯-醋酸乙烯酯，聚甲基丙烯酸正丁酯）。模型药物将包括伊曲康唑和灰黄霉素（与口服给药聚合物联合），地塞米松和纳曲酮（与可生物降解聚合物联合），西罗莫司和紫杉醇（与器械涂层聚合物联合）。通过改变制造和配方条件，可以得到分子分散、纳米分散和微分散的体系。不同厚度的样品将使用（低温）切片机以及自旋涂布机制备。它们的厚度将被确定，并将使用纳米红外光谱对它们进行表征。将评估样品厚度和测量条件对空间分辨率的影响。这将产生一个通用的优化采样协议，通过该协议可以实现最大的空间分辨率。在优化的采样条件下，采用先进的数据处理技术，将进一步提高该技术的化学分辨率。单变量和多变量分析将用于具有不同分散状态的药物-聚合物体系。使用确定的数据处理技术来产生最大的化学分辨率，将使制造和配方对结果分散的影响合理化。

DESCRIPTION (provided by applicant): In this project, the breakthrough new technique of nanoscale infrared (IR) spectroscopy, pioneered by Anasys Instruments, will be adapted and refined for Pharmaceutical and biological systems. The technique has numerous applications such as Polymorph screening; sub-cellular spectroscopy and Drug-Polymer composites. In this research proposal, we will focus on demonstrating proof of concept of the nanoscale IR platform to fully characterize the micro- and nanostructure of drug- polymer systems where Prof Taylor of Purdue is an expert. The measurement technique is based on the capability of an atomic force microscope (AFM) probe to detect the thermal expansion of samples in contact with an attenuated total reflectance (ATR) prism, following absorption of evanescent mid-IR waves. Using the technique, both localized mid-IR spectra as well as images collected at a specific wavelength can be obtained. This breakthrough technique has the potential to fully characterize the micro- and nanostructure of drug-polymer systems. Hence, an in-depth understanding of the dispersion state of the systems can be obtained. This can fill the current gap in understanding the relationship between manufacturing and formulation variables and resulting product performance of drug-polymer systems. The project aims at maximizing both spatial (the resolution associated with the imaging process as such) and chemical (the ability to chemically differentiate domains based on subsequent analytical processing of imaging data) resolution of the technique. The model systems selected will consist of a representative set of drug-polymer composites. The model polymers will cover a range of polymer types including those used for oral delivery (polyethylene oxide, cellulose based polymers), biodegradable polymers (polylactic acid, polylactic glycolic acid), and non-erodable device coating polymers (polyethylene-co-vinylacetate, poly n-butyl methacrylate). Model drugs will include itraconazole and griseofulvin (combined with oral delivery polymers), dexamethasone and naltrexone (combined with biodegradable polymers), and sirolimus and paclitaxel (combined with device coating polymers). By varying manufacturing and formulation conditions, molecularly, nano- and microdispersed systems will be obtained. Samples of varying thickness will be prepared using a (cryogenic) microtome as well as with a spin-coater. Their thickness will be determined and they will be characterized using nanoscale infrared spectroscopy. The effects of sample thickness and measurement conditions on spatial resolution will be evaluated. This will result in a general optimized sampling protocol by which a maximum spatial resolution can be achieved. Using these optimized sampling conditions, chemical resolution of the technique will be further improved by applying advanced data processing techniques. Uni- and multivariate analysis will be employed on drug-polymer systems with different dispersion states. Using the data processing techniques identified to generate maximized chemical resolution, the influence of manufacturing and formulation on resulting dispersion will be rationalized. PUBLIC HEALTH RELEVANCE: In this project, the breakthrough new technique of nanoscale infrared (IR) spectroscopy, pioneered by Anasys Instruments, will be adapted and refined for Pharmaceutical and biological systems. The technique has numerous applications such as Polymorph screening; sub-cellular spectroscopy and Drug- Polymer composites. In this research proposal, we will focus on demonstrating proof of concept of the nanoscale IR platform to fully characterize the micro- and nanostructure of drug-polymer systems where Prof Taylor of Purdue is an expert.