Abstract
The opioid epidemic in the United States is a serious public health crisis affecting over 1.7 million Americans. In the last two decades, almost 450 »000 people have died from an opioid overdose, with nearly 20% of these deaths occurring in 2017 and 2018 alone. During an overdose, overstimulation of the μ-opioid receptor leads to severe and potentially fatal respiratory depression. Naloxone is a competitive μ-opioid-receptor antagonist that is widely used to displace opioids and rescue from an overdose. Here, we describe the development of a slow-release, subcutaneous naloxone formulation for potential management of opioid overdose, chronic pain, and opioid-induced constipation. Naloxone is loaded into self-assembling peptide hydrogels for controlled drug release. The mechanical, chemical, and structural properties of the nanofibrous hydrogel enable subcutaneous administration and slow, diffusion-based release kinetics of naloxone over 30 days in vitro. The naloxone hydrogel scaffold showed cytocompatibility and did not alter the β-sheet secondary structure or thixotropic properties characteristic of self-assembling peptide hydrogels. Our results show that this biocompatible and injectable self-assembling peptide hydrogel may be useful as a vehicle for tunable, sustained release of therapeutic naloxone. This therapy may be particularly suited for preventing renarcotization in patients who refuse additional medical assistance following an overdose.
Original language | English (US) |
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Pages (from-to) | 7858-7864 |
Number of pages | 7 |
Journal | ACS Applied Bio Materials |
Volume | 3 |
Issue number | 11 |
DOIs | |
State | Published - Nov 16 2020 |
All Science Journal Classification (ASJC) codes
- General Chemistry
- Biochemistry, medical
- Biomedical Engineering
- Biomaterials
Keywords
- hydrogel
- naloxone release
- opioid addiction management
- peptide nanofibers
- self-assembly