Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: The goal of this project design and development of multifunctional nanomedicines to address unique and complex therapeutic outcomes in transplantation and organ preservation. Presented innovative methodology adopts quality-by-design to design, development and optimization of nanomedicine with multiple goals: imaging inflammation and organ rejection non-invasively, provide optimal oxygen delivery and deliver therapeutic entities (e.g. immunosuppressive agents, anti-inflammatory drugs, reactive oxygen species scavengers, anti-oxidants). Perfluorocarbons (PFCs) are useful platform material for theranostic nanomedicines as they are biologically inert reagents that can be quantitatively detected in vivo by 19F MRI and NMR, can be engineered to carry drugs with controlled release, carry additional imaging agents and sensors, and they have inherent oxygen delivery capacity useful in tissue and organ preservation.
*Methods: All presented formulation processes are designed to allow for future GMP grade manufacturing scale to support rapid clinical translation. Select critical quality attributes (CQAs), such as droplet size distribution, zeta potential, pH, drug content, and drug release will be monitored over time to evaluate product stability. In earlier studies, we demonstrated that theranostic nanocolloids could be scaled up to one liter with maintained CQAs. JMP statistical software will be used for all formulations (NEs and MENDS gels), design of experiments, and statistical modeling as reported earlier. Critical process parameters (CPPs). Oxygen carrying capacity was examined with a polarographic dissolved oxygen probe under optimized conditions. Biodistribuition and imaging capacity of these agents in varied rodent models, from chronic inflammation mouse model to transplant models in rats was evaluated using multimodal imaging.
*Results: Robust theranostic nanomedicine platform was created. Predictive mathematical models have been applied to nanomedicine manufacturing optimization and quality control. Drug delivery and imaging capacity was demonstrated in multiple rodent models of injury, inflammation and organ rejection. Pharmacological testing in vitro demonstrated anty-inflammatory and ROS scavenging effects in vitro. Successful and controlled oxygen loading and release was demonstrated in vitro.
*Conclusions: Nanomedicine in transplant and regenerative medicine is vastly underutilized. One of the reasons is complexity of therapeutic needs and lack of high quality manufacturing strategies to meet those needs. We demonstrated that quality-by-design approaches can be successfully applied to nanomedicines for achieving multiple therapeutic goals.
To cite this abstract in AMA style:Janjic JM, Lambert E, Liu L, Herneisey M, Gorantla VS. Multimodal Theranostic Nanocolloid Platform for Imaging, Targeted Drug Delivery and Organ Preservation in Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/multimodal-theranostic-nanocolloid-platform-for-imaging-targeted-drug-delivery-and-organ-preservation-in-transplantation/. Accessed September 27, 2021.
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