EFRI DCheM: Distributed Manufacturing of Personalized Medicines

EFRI DCheM：个性化药品的分布式制造

• 批准号: 2029139
• 负责人: Max Shtein
• 金额: $ 200万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029139&HistoricalAwards=false
• 关键词: EFRI; DCheM; Distributed; Manufacturing; Personalized

On a dollar per mass basis, active pharmaceutical ingredients (APIs) are perhaps the most valuable chemicals in the world, and yet much of the mass of APIs in drugs taken is not absorbed in the body, entering the water supply and potentially harming human health and the environment. At the same time, despite rapid advances in the science of personalized medicine, and digital, additive manufacturing, the trillion-dollar-per-year pharmaceutical industry retains its century-old manufacturing processes and uses supply chain and distribution models that are potentially prone to tampering, contamination, and disruption. To address this problem, researchers and drug manufacturers have begun developing 3D printing approaches, as well as techniques borrowed from other industries (e.g. thin-film coatings) for drug formulation, dose customization, and release profile engineering. However, fundamental challenges remain with material compatibilities, ingredient dispersion in solvents or matrix materials, process control, and scalability. This fundamental research project aims to address these challenges by converging several new breakthroughs in additive manufacturing, molecular and crystallization modeling, surface science and engineering, and patient-specific in vitro disease models. This project will train students of diverse backgrounds, including women and minorities, and those concerned with patient care and safety, public health, drug costs, regulatory law and practices.This fundamental research project will introduce a radically new approach to drug formulation and distributed manufacturing, offering new means of controlling crystalline structure, cocrystallization, and adaptation to different delivery vehicles. Currently, predictive model-based process design for organic crystallization processes is still in relative infancy. Likewise, processes for cocrystallization require further work to systematize coformer selection and prediction of conditions for cocrystal formation. The novel, solvent-free process used here offers possibilities for developing novel pharmaceutical cocrystallization research tools, as well as a path to scalable cocrystal manufacturing. The technology platform of controlled surface wettability patterns to enable low-cost dissolution assays, combined with the organoid assays will create new paradigms for on-site validation and control of product quality, which will be particularly beneficial in a distributed manufacturing setting. The organoid assays used could enable rapid testing of new medications in more realistic cellular microenvironments prior to human trials. This research will facilitate the path to accelerating the time from drug development to manufacturing and distribution, and help prevent potentially dangerous by-products or contaminants from reaching patients.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.

以每种质量为单位的美元，活性药物成分（API）也许是世界上最有价值的化学物质，然而，服用药物中的大量API并未吸收在体内，进入水供应并潜在地损害人类健康和环境。同时，尽管个性化医学的科学以及数字化，添加剂制造业的迅速发展，但每年数万亿美元的制药行业仍保留其具有百年历史的制造过程，并使用供应链和配送模型，这些供应链和配送模型可能很容易容易发生篡改，污染和破坏。为了解决这个问题，研究人员和药物制造商已开始开发3D打印方法，以及从其他行业（例如薄膜涂料）借用的用于药物制定，定制剂量和发布概况工程的技术。但是，基本挑战仍然存在着材料兼容性，溶剂或基质材料中的成分分散，过程控制和可扩展性。这个基本的研究项目旨在通过在添加剂制造，分子和结晶建模，表面科学和工程以及特定于患者的体外疾病模型中融合几个新的突破来应对这些挑战。该项目将培训各种背景的学生，包括妇女和少数群体，以及与患者护理和安全，公共卫生，药物成本，监管法律和实践有关的学生。这项基本研究项目将引入一种彻底的新方法来制定药物制定和分布式制造，提供新的手段，用于控制结构结构，共晶和对不同递送车辆的适应。当前，有机结晶过程的基于预测模型的过程设​​计仍处于相对婴儿期。同样，共晶的过程需要进一步的工作来系统化辅助选择和预测共晶形成的条件。这里使用的新型无溶剂工艺为开发新型药物共晶研究工具提供了可能性，以及可扩展共晶制造的途径。可控的表面润湿性模式的技术平台可实现低成本溶解测定，结合器官测定法会为现场验证和对产品质量的控制创造新的范式，这将在分布式制造环境中尤其有益。使用的类器官可以在人类试验之前在更现实的细胞微环境中快速测试新药物。这项研究将促进加速从药物开发到制造和分发时间的时间，并有助于防止潜在的危险副产品或污染物到达患者。该奖项反映了NSF的法定任务，并被认为是通过使用基金会的评估来支持的，并被认为是值得的。智力优点和更广泛的影响审查标准。

项目成果

Personalized models of heterogeneous 3D epithelial tumor microenvironments: Ovarian cancer as a model.

• DOI: 10.1016/j.actbio.2021.04.041
• 发表时间: 2021-09-15
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Horst EN;Bregenzer ME;Mehta P;Snyder CS;Repetto T;Yang-Hartwich Y;Mehta G
• 通讯作者: Mehta G

Gas-Assisted Cocrystal Desublimation

• DOI: 10.1021/acs.cgd.1c01241
• 发表时间: 2022-02
• 期刊: Crystal Growth & Design
• 影响因子: 3.8
• 作者: Shea Sanvordenker;Siddharth Borsadia;Steven A. Morris;N. Rodríguez-Hornedo;M. Shtein

Injectable three-dimensional tumor microenvironments to study mechanobiology in ovarian cancer.

• DOI: 10.1016/j.actbio.2022.04.039
• 发表时间: 2022-07-01
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Horst, Eric N.;Novak, Caymen M.;Burkhard, Kathleen;Snyder, Catherine S.;Verma, Rhea;Crochran, Darel E.;Geza, Izabella A.;Fermanich, Wesley;Mehta, Pooja;Schlautman, Denise C.;Tran, Linh A.;Brezenger, Michael E.;Mehta, Geeta
• 通讯作者: Mehta, Geeta