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On-Demand Opioid Effect Reversal with an Injectable Light-Triggered Polymer-Naloxone Conjugate
Wei Zhang1, Dali Wang1, Claire A Ostertag-Hill1
1Laboratory for Biomaterials and Drug Delivery, The Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Abstract:
Misuse of opioids can lead to a potential lethal overdose. Timely administration of naloxone is critical for survival. Here, we designed a polymer-naloxone conjugate that can provide on-demand phototriggered opioid reversal. Naloxone was attached to the polymer poly(lactic-co-glycolic acid) via a photocleavable coumarin linkage and formulated as injectable nanoparticles. In the absence of irradiation, the formulation did not release naloxone. Upon irradiation with blue (400 nm) light, the nanoparticles released free naloxone, reversing the effect of morphine in mice. Such triggered events could be performed days and weeks after the initial administration of the nanoparticles and could be performed repeatedly.
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