Seminar: Understanding the Effects of Human Lipoprotiens on Polymer Micelle Stability in Human Fluids

Seminar given by Timothy Langridge, Ph.D. candidate

Advisor: Dr. Richard Gemeinhart

Biopharmaceutical Sciences, UIC

Abstract: Polymer micelles are promising drug delivery systems for hydrophobic APIs. Despite several decades of research, these drug delivery vehicles have found limited success in translation from bench side to the clinic. This disparity is due, in part, to a limited understanding of the effects of the biological milieu on micelle stability in the fluid compartments of the body. Utilizing Förster resonance energy transfer (FRET), we have observed that block copolymer micelles composed of poly(ethylene glycol–block–d,l-lactide) and poly(ethylene glycol–block–ε-caprolactone) show variable instability across a panel of human fluids. Several different fluids were examined based on the potential as delivery routes, specifically intra-articular (synovial), peritoneal (ascites), pleural cavity (pleural), intra-cranial (cerebrospinal), cardiac (pericardial), and serum (fetal bovine serum). Blood is known to be a significant barrier toward efficacious micelle delivery, with destabilizing effects based on the most abundant proteins dependent on material chemistry. However, the body’s natural system for hydrophobic molecule transport, lipoproteins, have largely been ignored. We have observed that lipoproteins exhibit significant destabilizing effects on micelles and propose that endogenous lipids also play a significant role in micelle instability within systemic circulation.