Dr. Steven Schwendeman Awarded FDA Grant to Investigate Peptide-Polymer Interactions in PLGA Microspheres
Steven Schwendeman, PhD’92, Chair and Ara G. Paul Professor of Pharmaceutical Sciences, has been awarded $500,000 by the United States Food and Drug Administration (FDA) for the investigation of peptide-polymer interactions in PLGA microspheres.
There is a scientific gap in the current understanding of how different formulations as well as raw material variables used to manufacture poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating peptides lead to differing levels of peptide-polymer interactions and peptide acylation during encapsulation, storage, and release in vitro and in vivo. Batch-to-batch variation and unpredictable acylation levels could lead to differences in pharmacokinetics (PK) and loss of bioequivalence of generic long-acting release (LAR) formulations seeking to mimic LAR products. Such differences in bioequivalence may lead to differences in safety and efficacy. A key factor leading to the loss of parent drug is the poorly defined interaction between the peptide and the polymer, which has been shown to be a precursor to the acylation reaction.
“LAR formulations based on PLGA provide important benefits to patients,” notes Dr. Schwendeman. “LARs reduce how often patients need to take their medicine. The LAR is injected once per week to twice per year depending on the LAR product instead of once or multiple times a day. Certain peptide drugs react chemically with the biodegradable polymer excipients in LARs, causing challenges to the bioequivalence of some generic LARs seeking to enter the market.”
“I’m attempting to understand the importance and scientific basis for these reactions,” continues Dr. Schwendeman. “That information may lead to improved FDA guidance for generic manufactures, and thus help improve the safety and efficacy of generic LARs for patients. This project builds on decades of research from our lab and it is great to see both our early and more recent work brought to bear to help the FDA and patients. The project is also a terrific way to train graduate students and postdocs as it encompasses many fundamental aspects of pharmaceutics, physical chemistry, and engineering applied to important peptide drugs and PLGA delivery carriers.”