A Medical Countermeasure Against Drugs of Abuse with Detoxifying Biomimetic “Nanosponge” Decoy Receptors Directed Against Opioid Drugs and Methamphetamines

Abstract

Synthetic highly potent opioids (e.g., Oxycodone, fentanyl, carfentanil, & acrylfentanyl) are emerging as both national security & health threats. Every 15 minutes in the US, a person dies after overdosing on opioids, constituting a national crisis that affects public health as well as social and economic welfare. For opioid overdose, naloxone, an opioid receptor antagonist, is, to date, the only life‐saving treatment based on its acute reversal of respiratory depression/arrest.3 Critically, naloxone’s actions are short‐acting: when the opioid receptor again becomes accessible, residual opiates in the peripheral circulation or in the tissues can enter the CNS & “re‐narcotize” the patient causing an acute recurrence of life‐threatening respiratory depression/arrest – often before the patient in the field has been stabilized in a high‐acuity center. As such, naloxone therapy has potentially fatal shortcomings. In 2019, rates of natural opioid overdose deaths leveled out, yet overdose death rates involving synthetic opioids like fentanyl, which is 50 to 100 times more potent than morphine, have continued to increase. A major concern is that naloxone treatment could be insufficient against these synthetic opioids, and fatal.We designed and developed an acute opioid drug detoxifying treatment for overdose of any type of opioid, natural or synthetic. Our treatment can be administered with naloxone to compensate for nalaxone deficiencies and uses an opioid‐targeted biomimetic “nanosponges” that absorb overdosed opioids in the body. Called “NarcoBondTM” these 100 nm diameter nanospheres are made from a mixture of cholesterol & synthetic choline‐based phospholipids that mimic the lipid bilayer cell membranes.NarcoBond’s multifunctional surface displays an optimized milieu of human membrane proteins isolated from: a) erythrocytes to increase half‐life in peripheral blood & circulation, b) neurons to increase binding affinity for opioid receptor, & c) purified Mu opioid receptors to bind opioids in circulation. The NarcoBond’s repertoire of native opioid receptors (“Decoy Receptors”) broadly binds & captures opioids from microenvironmental niches of cells in tissues & blood resulting in an antagonistic pharmacological effect by rapidly reducing the concentration of the overdosed opioid.Our most recent in‐vitro and in‐vivo results, using this proteolipid nanosponge for detoxification of opioids, and our future plans for detoxification of methamphetamines using the same decoy receptor approach, will be presented. We will also present results of an informal survey of high school and college students (15–24 years of age), on intervention and adoption of countermeasures such as Naloxone and NarcoBond, in order to decrease the risk of licit and illicit drug overdose complications and fatalities.Support or Funding InformationNational Institute for Drug Abuse (NIDA)