Project Background

Extracorporeal membrane oxygenation (ECMO) is a lifesaving technology in critically ill patients. It's a cardiopulmonary bypass device that provides life-saving complete respiratory and cardiac support in patients with cardiorespiratory failure. Although this mechanical support can be life-saving, mortality often exceeds 40%. The high mortality is suspected to be due, in part, to significantly altered drug disposition by the ECMO circuit, resulting in suboptimal dosing. Dosing is different in this population because ECMO can alter drug pharmacokinetics (PK). The PK of drugs in patients on ECMO can be altered by 1) physiologic alterations triggered by the circuit and underlying critical illness and 2) direct interaction of the drug with the ECMO circuit via hydrophobic interactions. Hydrophobic drugs are extremely vulnerable to getting adsorbed on the ECMO circuits. Adsorption of drugs can be prevented by micellar encapsulation of drugs. The advantage of having a hydrophilic shell in micelles is that it will avoid the interactions of drugs with the hydrophobic ECMO circuit and charged ECMO surface coating, hence reducing the extent of adsorption of drugs on the ECMO circuit.

Student Role

In this project we are developing formulations by encapsulating hydrophobic drugs in micelles and testing the reduction of adsorption of drugs in ECMO circuits. Encapsulation with a generally recognized as safe (GRAS) micellar platform aids in the rapid translation to clinical practice.
The student will learn how to manufacture the micellar-drug nanoparticle formulations, how to measure their size, shape, stability and other physiochemical properties. They will perform these experiments to obtain batches of micellar-drug nanoparticle formulations. Then, the student will learn how to test the biocompatibility of these formulations in in-vitro and ex-vivo systems. This entails testing the micellar-drug nanoparticle formulations in human cells (in-vitro) and human blood (ex-vivo) for their biocompatibility and adsorption on ECMO circuits.

These experiments provide a wide range of experience for the student in a wet lab setting. Learning how to manufacture nanoparticles, how to characterize nanoparticles, learning good practices for cell culture handling, working with clinicians for testing nanoparticles in actual ECMO circuits etc. are a few examples.

Student Learning Outcomes and Benefits

In addition to wet lab experience, this project will also provide a knowledge base for the student in the field of drug delivery and pharmaceutics and how to bridge that knowledge in a clinical setting or how that knowledge can help in improving patient quality of life. Anyone who is particularly interested in performing research at the interface of basic research and a clinical setting would highly benefit from this project.

Gaining these skills can be very helpful for an undergraduate student, especially if they are planning to go further for graduate studies. Learning skills like literature review, giving presentations, being part of a research group, hands-on experience with experiments are some skills that every graduate student needs to learn for a successful transition from undergraduate to graduate studies and this project will help provide those skills.