Aromatic polypeptide amphiphiles for drug adsorption: a new approach for drug overdose treatment

Abstract

The drug overdose epidemic in America has intensified over the past 20 years and has led to hundreds of thousands of deaths. Opioids account for most of these deaths, but overdose can be effectively reversed using naloxone, an FDA-approved medication. The rate of non-opioid drug fatalities has also risen in recent years—but unlike opioids—many of these drugs do not have specialized treatments in cases of overdose. Instead, activated charcoal is ingested to decontaminate the gastrointestinal tract before the drug is absorbed by the blood. Although activated charcoal is an effective drug adsorbent, there are many adverse side effects following respiratory and oral exposure. To address the drawbacks of this treatment, a new class of aromatic polypeptide amphiphiles (termed “KEYs”) were developed to adsorb drugs from the stomach and intestines without harmful side effects. This manuscript details the rational design and synthesis of KEY polypeptide adsorbents. KEYs were evaluated against model compounds acid yellow 3 and amitriptyline in simulated biological media and compared to activated charcoal. Adsorption studies indicate that KEYs are capable of adsorbing drugs. KEYs adsorb molecules as rapidly as activated charcoal and adsorb certain compounds with comparable or higher adsorption capacity in a pH-dependent manner. This work represents a novel application of aromatic polypeptide amphiphiles as a gastrointestinal decontamination technology. Further, these studies provide insight for how future generations of polypeptide-based adsorbents can be rationally designed to selectively target and improve drug adsorption from the gastrointestinal tract.