PFI:AIR - TT: Novel Nanoprinting for Oral Delivery of Poorly Soluble Drugs

PFI:AIR - TT：用于难溶性药物口服给药的新型纳米打印

• 批准号: 1543056
• 负责人: Ahmed Busnaina
• 金额: $ 19.87万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1543056&HistoricalAwards=false
• 关键词: PFI; AIR; TT; Novel; Nanoprinting

This PFI: AIR Technology Translation project focuses on translating nanoscale 3D printing technology to enable oral preparation of poorly soluble drugs. The novel drug 3D nanoprinting process, developed at the NSF Center for High Rate Nanomanufacturing, is important because it will enable oral administration of various promising drug candidates that currently can only be given intravenously. This will increase patient compliance and decrease the time and cost involved in therapy, while enhancing drug safety from the development-to-patient process. The project will result in a proof-of-concept for an entirely new drug nanoprinting technology for controlled and effective delivery of poorly soluble drugs via oral administration. This technology has the following unique features. The research will print drug-loaded polymeric micelles into 100nm or smaller size nanorods with well-defined shapes. The precise control of the size and shape of the nanorods will provide a sufficiently high and fixed drug dosage in the blood to get a desired therapeutic response. The 3-D drug-loaded nanorods will be embedded into a unique polymer that can only dissolve at a specific basic pH that can be chosen based on the desired location for the drug release in the body. For example, the drug nanorods can be released in the intestine after passing through the stomach, and this also eliminates the stability issue due to pH variation in the GI track. Due to their small size, these nanorods will have a high permeability, thus enabling effective transport through the intestinal wall as compared to spheres or other shapes. In addition, the drug nanorods are expected to penetrate tumors more efficiently and much faster than spherical drug nanoparticles. This should lead to a better bioavailability of the drug with reduced toxicity and side effects. The printing technique will also enable the preparation of multi-drug nanorods, where the nanorods can be composed of several poorly soluble drugs to overcome multi-drug resistance. These features will enable effective intracellular penetration through the intestine and controlled oral administration of poorly soluble drugs when compared to drugs such as micellar paclitaxel and free paclitaxel in this market space. This project addresses the following technology gap(s) as it translates from research discovery toward commercial application. Various sub 100nm diameter nanorods will be characterized for their in vitro permeability to develop a fundamental understanding of the effect of nanorod size and aspect ratio on the cell penetration. The proposed research will evaluate and characterize in vitro cytotoxicity of the printed drug-loaded micellar nanorods in cancer cells to determine the sufficiently high level of these drugs in the blood to get a desired therapeutic response. The research will also investigate the effect of size and shape of the nanorods on internalization by the cancer cells. In addition, personnel involved in this project, undergraduates and graduates students, will receive innovation, educational and entrepreneurial experiences through interaction with pharmaceutical companies, mentoring sessions, and entrepreneurship courses provided at Northeastern University.

该 PFI：AIR 技术翻译项目专注于将纳米级 3D 打印技术转化为难溶性药物的口服制剂。 NSF 高速纳米制造中心开发的新型药物 3D 纳米打印工艺非常重要，因为它将使目前只能静脉注射的各种有前景的候选药物能够口服给药。这将提高患者的依从性，减少治疗的时间和成本，同时增强从开发到患者过程的药物安全性。该项目将对一种全新的药物纳米打印技术进行概念验证，用于通过口服给药控制和有效地输送难溶性药物。该技术具有以下独特的特点。该研究将载药聚合物胶束打印成 100 纳米或更小尺寸、形状明确的纳米棒。对纳米棒尺寸和形状的精确控制将在血液中提供足够高且固定的药物剂量，以获得所需的治疗反应。 3-D 载药纳米棒将嵌入一种独特的聚合物中，该聚合物只能在特定的碱性 pH 值下溶解，可根据体内药物释放的所需位置进行选择。例如，药物纳米棒通过胃后可以在肠道中释放，这也消除了由于胃肠道pH变化而导致的稳定性问题。由于尺寸小，这些纳米棒具有高渗透性，因此与球体或其他形状相比，能够有效地穿过肠壁运输。此外，药物纳米棒有望比球形药物纳米颗粒更有效、更快地穿透肿瘤。这应该会导致药物具有更好的生物利用度，同时降低毒性和副作用。该打印技术还将能够制备多药纳米棒，其中纳米棒可以由几种难溶性药物组成，以克服多药耐药性。与该市场领域的胶束紫杉醇和游离紫杉醇等药物相比，这些特征将能够有效地穿过肠道进行细胞内渗透，并控制难溶性药物的口服给药。该项目在从研究发现转向商业应用的过程中解决了以下技术差距。各种亚 100 纳米直径纳米棒的体外渗透性将得到表征，以便从根本上了解纳米棒尺寸和长宽比对细胞渗透的影响。拟议的研究将评估和表征印刷的载药胶束纳米棒在癌细胞中的体外细胞毒性，以确定这些药物在血液中足够高的水平以获得所需的治疗反应。该研究还将研究纳米棒的尺寸和形状对癌细胞内化的影响。此外，参与该项目的本科生和研究生人员将通过东北大学提供的与制药公司的互动、辅导课程和创业课程来获得创新、教育和创业经验。