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

Northeastern University, Boston MA

Investigators

Abstract

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.