Overall Lab Objective
Our research focuses on cell adhesion and drug delivery. Specifically, we are utilizing the physiological and cellular response to inflammation and corresponding blood hemodynamics to design bio-functionalized particles for targeted drug delivery and imaging.
Particle Behavior in Blood Flow
Particle size is an important parameter that would dictate the binding efficiency of drug carriers to the vascular wall. To date, little work has been done on determining an optimal size of these carriers in whole blood - past research has primarily focused on particle behavior in saline buffer looking at sizes ranging from nanometers to microns. The lab is interested in how particle size and hemodynamics and rheology prescribe the ability of drug carriers to interact with the vascular wall.
Drug Carrier Design
Recent literature suggests non-spherical particles may by ideal for certain vascular-targeted drug delivery applications. Thus, we manipulated the well-described oil-in-water solvent evaporation method to fabricate spheroidal particles from the biodegradable polymer Poly(lactic-co-glycolide) (PLGA).
Size, shape and surface characteristics of the microparticles can be controlled by varying parameters during fabrication such as aqueous buffer viscosity and pH, oil phase viscosity and shear rate.
Adhesion of Spheroidal Particles In Vitro and In Vivo
Previous studies demonstrated that ellipsoidal particles drift towards a wall in a parallel plate flow setup. The plausible particle drift towards the wall depends on the micro-environment, aspect ratio, shear stress etc. We study the role of shear stress on stretched particle binding in a parallel plate flow chamber. Our research is focused on understanding the hemodynamic interactions of these ellipsoidal particles for potential vascular-targeted drug delivery applications.
In Vivo Targeting of Ligand-Conjugated Microparticles to Atherosclerotic Plaques
Supriya Mocherla, Dana Matthews
In collaborative work with Dr. Pinksy's Cardiovascular Research Lab at the University of Michigan's Medical School, we are studying the localization of fluorescent polystyrene ellipsoidal and spheroidal microparticles injected into aortas of mice with significantly progressed atherosclerotic lesions. This research will help us better understand the behavior of both types of particles in an in vivo environment.
The study of receptor interactions between inflamed endothelium and neutrophil is critical to understanding the mechanics behind transmigration. Using in vitro models of vascular tissue and laminar flow assays, environments mimicking the types of shear forces experienced by the endothelium can be simulated; quantification of receptor interactions under inflammatory conditions will then allow for modeling the binding kinetics between cell/neutrophil ligands. By determining the receptor expression frequency under various types of shear, appropriate targets for polymeric cell drug carriers are identified.
Literature has not completely elucidated the mechanism of neutrophil transmigration. Understanding this process can better aid in designing drug carriers. Evidence suggest neutrophil transmigration into injured cornea tissue involves interaction with blood platelets. The main aim of this project is to investigate the effect of platelets on neutrophil transmigration and understand platelet-endothelial interaction during inflammation.