Work

Microphysiological system to address the opioid crisis: A novel multi-organ model of acute opioid overdose and recovery

Year: 2024

Type: article

Abstract: • Opioid overdose has been named a public health crisis as of 2017 by the CDC. • Naloxone is currently the main compound used to treat opioid overdose. • The off-target toxicity of naloxone has yet to be investigated. • Here a microphysiological system is used to model opioid overdose and recovery. • This model can be used to test efficacy and toxicity of new overdose treatments. Opioids have been the primary method used to manage pain for hundreds of years, however the increasing prescription rate of these drugs in the modern world has led to a public health crisis of overdose related deaths. Naloxone is the current standard treatment for opioid overdose rescue, but it has not been fully investigated for potential off-target toxicity effects. The current methods for pharmaceutical development do not correlate well with pre-clinical animal studies compared to clinical results, creating a need for improved methods for therapeutic evaluation. Microphysiological systems (MPS) are a rapidly growing field, and the FDA has accepted this area of research to address this concern, offering a promising alternative to traditional animal models. This study establishes a novel multi-organ MPS model of acute opioid overdose and rescue to investigate the efficacy and off-target toxicity of naloxone in combination with opioids. By integrating primary human and human induced pluripotent stem cell (hiPSC)-derived cells, including preBötzinger complex neurons, liver, cardiac, and skeletal muscle components, this study establishes a novel functional multi-organ MPS model of acute opioid overdose and rescue to investigate the efficacy and off-target toxicity of naloxone in combination with opioids, with clinically relevant functional readouts of organ function. The system was able to successfully exhibit opioid overdose using methadone, as well as rescue using naloxone evidenced by the neuronal component activity. In addition to efficacy, the multi-organ platform was able to characterize potential off-target toxicity effects of naloxone, specifically in the cardiac component.

Source: Current Research in Toxicology

DOI: 10.1016/j.crtox.2024.100209