Development of Scale-Up Manufacturing of ‘INCeRT’ Implants for Localized Tumor Delivery of Chemotherapeutics

Presenter: Sanahan Vijayakumar

Research Category: Interdisciplinary Topics, Centers and Institutes
Student Type: Graduate
Additional Authors: Neha Shankar, Bijay Singh, Srinivas Sridhar
PI: Sanahan Vijayakumar
Faculty Advisor: Srinivas Sridhar
Award Winner Category: Interdisciplinary Topics

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men, with 26,730 deaths in the US in 2017, requiring new treatment options. One approach for PCa treatment is brachytherapy, which uses radioactive seeds deposited in the prostate gland to release controlled and localized radiation. The current form of brachytherapy utilizes plastic inert spacers to place radioactive seeds in the prostate. We have earlier synthesized biocompatible and biodegradable polymer-based “smart” Implantable Nanoplatform for Chemo-radiation Therapy (INCeRT) spacers that combines radiation therapy and targeted drug delivery. These spacers are fabricated as a chemo-toxic agent, Docetaxel (DTX), loaded Poly(lactic-co-glycolic) acid (PLGA) cylindrical implant usable in brachytherapy procedures.

Previous research has demonstrated the success of spacers fabricated from a mixture of PLGA, DTX, and a solvent. However, the development of solvent-free DTX-loaded PLGA spacers is considered a significant improvement for pharmaceutical grade manufacturing, that is critically needed for translation to the clinic. The mechanistic effects of hot melt extrusion, a pharmaceutical process used to develop polymer-based drugs of uniform shape and density, is analyzed through rheology and calorimetry for successful extrusion of biocompatible spacers by taking advantage of the low glass transition temperature of PLGA. In-vitro and in-vivo experiments of rodent models will help determine the efficacy of solvent-free spacers. This novel PCa therapeutic strategy would benefit patients by substantially yielding higher survival rates, improved targeted drug delivery while avoiding systemic toxicity.

Partially supported by 1R41CA224646-0.