Development of a new Imaging Platform for Pharmaceutical and Biomedical applicati

描述(申请人提供)：在这个项目中，由Anasys仪器公司首创的突破性纳米级红外(IR)光谱新技术将被应用于制药和生物系统。这项技术有许多应用，如多晶型筛选、亚细胞光谱和药物-聚合物复合材料。在这项研究提案中，我们将重点展示纳米级IR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，普渡大学的泰勒教授是这方面的专家。该测量技术基于原子力显微镜(AFM)探头的能力，该探头可以检测样品在吸收消逝的中红外波后与衰减全反射(ATR)棱镜接触时的热膨胀。使用该技术，既可以获得局部化的中红外光谱，也可以获得在特定波长采集的图像。这项突破性的技术有可能充分表征药物-聚合物系统的微结构和纳米结构。因此，可以对系统的色散状态有一个深入的了解。这可以填补目前在了解药物-聚合物系统的制造和配方变量之间的关系以及由此产生的产品性能方面的空白。该项目旨在最大限度地提高该技术的空间分辨率(与成像过程相关的分辨率)和化学分辨率(根据随后的成像数据分析处理在化学上区分区域的能力)。选定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。模型聚合物将涵盖一系列聚合物类型，包括用于口服的聚合物(聚环氧乙烷、纤维素基聚合物)、可生物降解的聚合物(聚乳酸、聚乳酸、聚乙醇酸)和不可擦除的设备涂层聚合物(聚乙烯-共-乙酸乙烯酯、聚甲基丙烯酸丁酯)。模型药物将包括伊曲康唑和灰黄霉素(与口服聚合物结合)，地塞米松和纳曲酮(与可生物降解聚合物结合)，以及西罗莫司和紫杉醇(与装置涂层聚合物结合)。通过改变制造和配方条件，将获得分子、纳米和微分散体系。不同厚度的样品将使用(低温)切割机和旋涂机进行制备。它们的厚度将被确定，并将使用纳米级红外光谱进行表征。将评估样品厚度和测量条件对空间分辨率的影响。这将导致一个通用的优化采样协议，通过该协议可以获得最大的空间分辨率。利用这些优化的采样条件，通过应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。对具有不同分散状态的药物-聚合物体系进行单变量和多变量分析。使用确定的数据处理技术来产生最大的化学分辨率，制造和配方对所产生的分散的影响将被合理化。 与公众健康相关：在这个项目中，由Anasys仪器公司首创的突破性纳米级红外(IR)光谱新技术将被改造和改进，用于制药和生物系统。这项技术有许多应用，如多晶型筛选、亚细胞光谱和药物-聚合物复合材料。在这项研究提案中，我们将重点展示纳米级IR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，普渡大学的泰勒教授是这方面的专家。

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.