Titanate nanotubes as an efficient oral detoxifying agent against drug overdose: application in rat acetaminophen poisoning

Abstract

Voluntary drug intoxication is mainly due to drug overdose or the interaction of several drugs. Coma and its associated complications such as hypoventilation, aspiration pneumopathy, and heart rhythm disorders are the main hallmarks of drug intoxication. Conventional detoxification treatments, including gastric lavage or vomiting, administration of ipecac or activated charcoal (CH), and the use of antidotes, have proven to be inefficient and are generally associated with severe adverse effects. To overcome these limitations, titanate nanotubes (TiNTs) are proposed as an efficient emerging detoxifying agent because of their tubular shape and high adsorption capacity. In the present study, the detoxifying ability of TiNTs was evaluated on paracetamol (PR)-intoxicated rats. Results indicate that the loading ability of PR into TiNTs (70%) was significantly higher than that recorded for CH (38.6%). In simulated intestinal medium, TiNTs showed a controlled drug release of less than 10% after 72 h of incubation. In PR-intoxicated rats, TiNTs treatment resulted in a 64% decrease of PR after 4 h of poisoning versus 40% for CH. Concomitantly, TiNTs efficiently reduced PR absorption by 90% after 24 h of poisoning, attenuated the elevated levels of biochemical markers (i.e., alanine aminotransferase, aspartate aminotransferase, creatinine, and TNF-α) and mitigated oxidative stress by increasing the activity of superoxide dismutase and reducing the oxidized glutathione/total glutathione ratio, suggesting a histoprotective effect of TiNTs against paracetamol-induced toxicity in rats. In addition to their safety and high stability in the entire gastro-intestinal tract, biodistribution analysis revealed that TiNTs exhibited low intestinal absorption owing to their large cluster size of compact aggregate nanomaterials across the intestinal villi hindering the absorption of paracetamol. Collectively, these data provide a new and promising solution for in vivo detoxification. TiNTs are expected to have great potential for the treatment of voluntary and accidental intoxication in emergency care.