Evaluation of Injectable Naloxone-Releasing Hydrogels

Kaytlyn M. Crowe, Zain Siddiqui, Victoria Harbour, Kakyung Kim, Shareef Syed, Reshma Paul, Abhishek Roy, Ruhi Naik, Kayla Mitchell, Aryan Mahajan, Biplab Sarkar, Vivek A. Kumar

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)7858-7864
Number of pages7
JournalACS Applied Bio Materials
Volume3
Issue number11
DOIs
StatePublished - Nov 16 2020

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

Keywords

  • hydrogel
  • naloxone release
  • opioid addiction management
  • peptide nanofibers
  • self-assembly

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