Document Type

Thesis

Date of Award

8-31-2021

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering

First Advisor

Vivek A. Kumar

Second Advisor

Rajesh N. Dave

Third Advisor

James Haorah

Abstract

Ease of access to prescription opioids and the strength of synthetic opioids have contributed to the rise in over use disorders, overdose, and death rates during the opioid epidemic. The current overdose standard of care, rescue NLX (NLX), is a competitive antagonist to the μ-opioid receptor but has a relatively short period of action compared to opioid agonists, especially synthetic agonists. Rises in the abuse of these synthetic and semi-synthetic agents in recent years have shown the weaknesses of rescue NLX, as it can leave overdose patients vulnerable to renarcotization and precipitated withdrawal. To prevent both from occurring, we developed a slow release, subcutaneous NLX-loaded peptide formulation for the potential management of renarcotization and precipitated withdrawal. We synthesized a series of multidomain peptides with and without loaded NLX and characterized their chemical, mechanical, and biophysical properties. The nanofibrous ultrastructure was assessed with atomic force microscopy (AFM), the secondary structure was probed by Fourier transform infrared spectroscopy in attenuated total reflectance mode (FTIR-ATF), β-sheet formation was confirmed with circular dichroism (CD), and the viscoelastic and thixotropic properties were measured via oscillatory rheometry. In vitro cytocompatibility of the peptides was investigated using 3T3 fibroblast cells and a CCK8 assay. To evaluate the long-term release viability of the peptides, an in vitro release study was performed for 7 and 30 days.

Share

COinS