Unraveling the Biomolecular Corona on Locally Delivered Nanomedicines

Project Summary The Biological Engineering for Advanced Drug Delivery (BEADD) Laboratory studies particle behavior in vitro and in vivo to develop improved local drug delivery formulations. Local drug delivery is optimal for treating ocular, respiratory, gastrointestinal, and vaginal indications, as it can increase drug concentration in local tissues while decreasing off-target side effects. Our previous work demonstrated that locally delivered formulations must be strategically designed to reach exposed epithelial surfaces in the human body. This rational design can lead to improved formulation uptake and therapeutic outcomes. Despite advances in designing locally delivered formulations, we do not yet have a thorough understanding of how proteins, lipids, and other biomolecules affect the stability, biodistribution, and uptake of locally delivered therapies. The adsorption of biomolecules onto a particle’s surface is known as the biomolecular corona and has been extensively studied for systemically administered formulations. However, we still do not fully grasp how particle physical properties (size, shape, surface chemistry) impact the formation of the biomolecular corona in other biological matrices (besides serum), nor is it clear how local environments affect corona formation or how the corona impacts particle behaviors in the body. This Early-Stage Investigator Maximizing Investigators Research Award (ESI MIRA) will employ a range of engineering tools to study the formation of the biomolecular corona on locally delivered particles and the resulting effect of the corona on particle stability, distribution, and uptake. Specifically, this ESI MIRA research program addresses three fundamental knowledge gaps surrounding the biomolecular corona on locally delivered particles: (1) How do particle physical properties affect surface adsorption of biomolecules; (2) how does the local microenvironment influence the formation of the biomolecular corona; and (3) how does the biomolecular corona impact particle stability, distribution, and uptake in vivo? The proposed work will leverage a robust particle library, human samples, proteomics and lipidomics, innovative multiple-particle tracking technology, and physiologically relevant animal models to unravel the formation of the biomolecular corona on locally delivered particles. Over the next five years, this ESI MIRA research program within the BEADD Lab will generate a fundamental understanding of the biomolecular corona and how it impacts locally delivered formulations. This work will establish the BEADD Lab as a leader in local drug delivery technologies and set the foundation for engineering next-generation precision therapies for treating a wide range of human health indications.