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

这个PFI：空气技术翻译项目专注于翻译纳米级3D打印技术，以使难溶药物的口服制剂成为可能。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给药的各种有希望的候选药物能够口服给药。这将提高患者的依从性，减少治疗所涉及的时间和成本，同时从开发到患者的过程提高药物安全性。该项目将为一种全新的药物纳米印刷技术带来概念验证，以控制和有效地通过口服给药输送难溶药物。这项技术具有以下独特的特点。这项研究将把载药聚合物胶束打印成形状明确的100 nm或更小尺寸的纳米棒。对纳米棒大小和形状的精确控制将在血液中提供足够高和固定的药物剂量，以获得所需的治疗反应。三维载药纳米棒将被嵌入到一种独特的聚合物中，该聚合物只能在特定的基本pH下溶解，该pH值可以根据药物在体内释放的所需位置来选择。例如，药物纳米棒可以在通过胃后在肠道中释放，这也消除了由于GI轨迹中的pH变化而造成的稳定性问题。由于它们的尺寸较小，这些纳米棒将具有高渗透性，因此与球体或其他形状相比，能够有效地通过肠壁进行运输。此外，药物纳米棒有望比球形药物纳米粒更有效、更快地穿透肿瘤。这应该会导致药物更好的生物利用度，降低毒性和副作用。印刷技术还将使多药物纳米棒的制备成为可能，其中纳米棒可以由几种难溶的药物组成，以克服多药耐药性。与这一市场空间中的胶束紫杉醇和游离紫杉醇等药物相比，这些特点将使难溶药物能够有效地通过肠道进行细胞内渗透和受控口服。该项目解决了以下技术差距(S)，因为它从研究发现转化为商业应用。各种直径小于100 nm的纳米棒将被表征其体外渗透性，以加深对纳米棒尺寸和长径比对细胞渗透的影响的基本了解。这项拟议的研究将评估和表征印刷药物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的足够高水平，以获得所需的治疗反应。这项研究还将调查纳米棒的大小和形状对癌细胞内化的影响。此外，参与该项目的人员，本科生和研究生，将通过与制药公司的互动、导师会议和东北大学提供的创业课程获得创新、教育和创业经验。

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.