Abstract
Opioid overdose accounts for nearly 75,000 deaths per year in the United States, now a leading cause of mortality among young people aged 18 to 45 years. At overdose levels, opioid-induced respiratory depression becomes fatal without the administration of naloxone within minutes. Currently, overdose survival relies on bystander intervention, requiring a nearby person to find the overdosed individual and have immediate access to naloxone to administer. To circumvent the bystander requirement, we developed the Naloximeter: a class of life-saving implantable devices that autonomously detect and treat overdose while simultaneously contacting first responders. We present three Naloximeter platforms, for fundamental research and clinical translation, all equipped with optical sensors, drug delivery mechanisms, and a supporting ecosystem of technology to counteract opioid-induced respiratory depression. In small and large animal studies, the Naloximeter rescues from otherwise fatal opioid overdose within minutes. This work introduces life-changing, clinically translatable technologies that can broadly benefit a susceptible population recovering from opioid use disorder.
| Original language | English (US) |
|---|---|
| Article number | eadr3567 |
| Journal | Science Advances |
| Volume | 10 |
| Issue number | 43 |
| DOIs | |
| State | Published - Oct 25 2024 |
Funding
We thank the members of the Rogers laboratory for useful discussions of the project, particularly S. Madhvapathy for advice on several aspects of device survivability. We also thank E. Dempsey, I. Stepien, N. Haack, and C. Haney for advice related to small animal experiments; H. Saleh, M. McIntyre, K. Dunlap, and C. Jones for assistance with large animal studies; and M. Park for preliminary efforts in device development. Swine studies were assisted by the Large Animal Surgical team in the Northwestern University (NU) Center for Comparative Medicine. This work made use of the NUFAB facility at the NUANCE Center, which has received support from the ShyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-2308691). Metal analysis for gadolinium PK studies was performed at the Quantitative Bio-element Imaging Center (QBIC, NU) generously supported by the NIH under grant S10OD020118. This work used the facilities of the High Throughput Analysis Laboratory (HTAL, NU) and the Center for Clinical Pharmacology at the University of Health Science and Pharmacy. Figures 1A and 4, A, D, G, and J, and figs. S11A and S21 were created with illustrations from Biorender.com. This work was supported by the National Institutes of Health through the HEAL Initiative (https://heal.nih.gov/) under award numbers UG3DA050303 and UH3DA050303 (to R.W.G. and J.A.R.). J.L.C. acknowledges support from the National Science Foundation Graduate Research Fellowship under grant no. DGE-2234667, A.V.-G. recognizes support from North Carolina State University under grant no. 201473-02139, and V.E.B. recognizes additional support from the National Institutes of Health under award T32GM108539. Acknowledgments: We thank the members of the Rogers laboratory for useful discussions of the project, particularly S. Madhvapathy for advice on several aspects of device survivability. We also thank e. dempsey, i. Stepien, n. haack, and C. haney for advice related to small animal experiments; h. Saleh, M. Mcintyre, K. dunlap, and C. Jones for assistance with large animal studies; and M. Park for preliminary efforts in device development. Swine studies were assisted by the large Animal Surgical team in the northwestern University (nU) Center for Comparative Medicine. this work made use of the nUFAB facility at the nUAnCe Center, which has received support from the Shyne Resource (nSF eCCS-2025633), the iin, and northwestern\u2019s MRSeC program (nSF dMR-2308691). Metal analysis for gadolinium PK studies was performed at the Quantitative Bio-element imaging Center (QBiC, nU) generously supported by the nih under grant S10Od020118. this work used the facilities of the high throughput Analysis laboratory (htAl, nU) and the Center for Clinical Pharmacology at the University of health Science and Pharmacy. Figures 1A and 4, A, d, G, and J, and figs. S11A and S21 were created with illustrations from Biorender.com. Funding: this work was supported by the national institutes of health through the heAl initiative (https://heal.nih.gov/) under award numbers UG3dA050303 and Uh3dA050303 (to R.W.G. and J.A.R.). J.l.C. acknowledges support from the national Science Foundation Graduate Research Fellowship under grant no. dGe-2234667, A.v.-G. recognizes support from north Carolina State University under grant no. 201473-02139, and v.e.B. recognizes additional support from the national institutes of health under award t32GM108539. Author contributions: Conceptualization: J.l.C., A.v.-G., J.A.R., R.W.G., and J.A.M. Methodology: J.l.C., A.v.-G., M.R.t., R.A.O., A.J.M., R.W.G., and J.A.R. Software: A.v.-G. and J.t. Formal analysis: J.l.C., A.v.-G., and v.e.B. investigation: J.l.C., A.v.-G., v.e.B., J.P., B.R., M.R.t., e.A.C., A.R.B., R.A.Sp., P.G., J.K., R.A., M.S., R.A.Sl., M.A.K., B.v.-h., n.M., and M.C.M. Resources: M.P., Y.h., J.A.M., J.A.R., and R.W.G. Writing\u2014original draft: J.l.C. and A.v.-G. Writing\u2014review and editing: J.l.C., A.v.-G., J.P., P.G., v.e.B., B.R., R.W.G., and J.A.R. visualization: J.l.C., A.v.-G., and J.P. Supervision and funding acquisition: J.A.R. and R.W.G. Competing interests: J.l.C., A.v.-G., v.e.B., B.R., J.A.M., R.W.G., and J.A.R. have submitted a patent application based on the research described in this manuscript (United States Patent Office no. PCt/ US2022/033093, June 2022). the other authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.
ASJC Scopus subject areas
- General
