Evaluation of Injectable Naloxone-Releasing Hydrogels

Document Type

Article

Publication Date

11-16-2020

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.

Identifier

85097061327 (Scopus)

Publication Title

ACS Applied Bio Materials

External Full Text Location

https://doi.org/10.1021/acsabm.0c01016

e-ISSN

25766422

First Page

7858

Last Page

7864

Issue

11

Volume

3

Grant

IIP 1903617

Fund Ref

National Science Foundation

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