PFI-TT: Research and Development of a Novel Printer for Small Molecular-Based Medicines That Enhances Their Dissolution Properties and Cost-Effectiveness.

该PFI项目的更广泛影响/商业潜力将是提高药物研究、开发和制造的速度和成本效益，最终降低新型复杂药物的成本，并使人们更容易服用对抗某些疾病所需的药物组合。目前在药物发现和生产方面的许多做法已经有一个世纪的历史，导致质量差、患者依从性差、可扩展性差以及许多药物的稀缺性。拟议的方法与制药部门的现有做法截然不同，增强了药物中活性成分的特性，降低了临床前测试所需的溶剂量，从而减少了有毒化学废物，但与许多现有药物和剂型（例如药片、凝胶帽、贴片、注射剂等）兼容。如果成功，该技术将缩短几年的药物开发时间，使多种药物更容易结合成一个单独的药丸或贴片为每个病人量身定制，并减少宝贵的活性成分的数量被浪费由于身体消除或未使用的处方药。拟议的项目具有重大的智力价值，因为它利用半导体工业和纳米技术来解决制药科学、开发和制造方面长期存在的问题。该项目的核心工艺可以精确和准确地打印活性药物成分（api），同时还可以增强其溶解性，而无需使用强溶剂或有毒溶剂。它将促进对药物化合物的热性质、分子结构和晶体结构之间的联系以及其对溶解性质和生物利用度的影响的理解。虽然某些化合物已经显示出这些能力，但它们仍然无法用于更广泛的制药研究界。这个多学科项目将使分子化学家、生物学家和药理学家广泛使用这种能力，使他们能够投入更多的时间来优化小分子疗法的效力和位点特异性结合，而不会面临溶解度瓶颈。这项提议的工作有望释放数百万种现成的合成化合物的治疗潜力，这些化合物由于溶解度差而在材料库中逐渐消失，并将利用深度学习和数据驱动的医学科学创造前所未有的复杂组合疗法。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this PFI project will be to enhance the rate and cost-effectiveness of pharmaceutical research, development and manufacturing, ultimately lowering the cost of new, sophisticated medicines, as well as making it easier for people to take combinations of medicines required to combat some diseases. Many current practices in drug discovery and manufacturing are century-old, resulting in poor quality, poor patient compliance, poor scalability, and scarcity of many medicines. The proposed approach differs radically from existing practices in the pharmaceutical sector, enhances the properties of active ingre-dients in medicines, drives down the amount of solvents required for pre-clinical testing and thus reducing toxic chemical waste, yet is compatible with many existing drugs and dosage forms (e.g. pills, gel caps, patches, injections, etc.). If successful, the proposed technology could short-en by several years the drug development timeline, make it easier to combine multiple med-icines into a single pill or patch tailored to each patient, and reduce the amount of precious active ingredient being wasted due to body elimination or unused prescription medicines. The proposed project has significant intellectual merit, in that it leverages techniques from the semiconductor industry and nanotechnology to address long-standing problems in pharmaceutical science, development, and manufacturing. The process at the core of this project can print active pharmaceutical ingredients (APIs) with precision and accuracy, while also enhancing their dissolution without resorting to strong or toxic solvents. It will advance understanding of thermal properties of pharmaceutical compounds, the link between molecular structure and crystal structure, and its influence on dissolution properties and bioa-vailability, which it enhances. While these capabilities have been shown for some compounds, they remain unavailable to the broader pharma research community. This multi-disciplinary project will make the capability widely available to molecular chemists, biologists, and pharmacologists, allowing them to devote more of their time to optimizing small molecular therapeutics for potency and site-specific binding, without facing solubility bottlenecks. The proposed work promises to unlock the therapeutic potential of millions of al-ready synthesized compounds that are languishing in material libraries due to their poor solubility, and to create combination therapies of unprecedented sophistication that will leverage deep learning- and data-driven medical science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.