title: Application of carbon nanotubes as the carriers of the cannabinoid, 2-arachidonoylglycerol: Towards a novel treatment strategy in colitis.
abstract: OBJECTIVE
  Treatment of colitis has remained a major clinical challenge. The cannabinoid, 2-arachidonoyglycerol (2-AG), has shown beneficial effects in colitis, however, poor solubility or rapid hydrolysis may limit its efficiency. According to the high biocompatibility of carbon nanotubes (CNTs) and their ability for controlled drug delivery, we aimed to prepare multi-walled CNTs-2-AG (MWCNTs-2-AG) complex in order to improve the pharmacological profile of 2-AG and evaluate the therapeutic potential of this nanocomplex in a rat model of colitis.
  
  
  METHODS
  Aminated MWCNTs-2-AG complex was prepared using acidified MWCNTs and then characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. In vitro cytotoxicity of MWCNTs was evaluated. Colitis was induced by colonic instillation of trinitrobenzene sulfonic acid (TNBS) and the effects of 2-AG solution and various types of MWCNTs on the colonic tissue damage, inflammation, and oxidative stress were evaluated.
  
  
  RESULTS
  Aminated MWCNTs and MWCNTs-2-AG complex exhibited significantly lower cytotoxicity than acidified MWCNTs. Once daily intrarectal application of MWCNTs-2-AG complex (containing 2mg/kg of 2-AG) 2days before and 8days after the induction of colitis effectively reduced the macroscopic and microscopic injuries, malondialdehyde, tumour necrosis factor-α, and interlukin-1β concentrations, and myeloperoxidase activity. While, free 2-AG (2mg/kg), and acidified or aminated MWCNTs showed no beneficial effects.
  
  
  CONCLUSIONS
  Amino-functionalized MWCNTs appear as the suitable carriers for 2-AG which provide a sustained concentration for this cannabinoid leading to the promising therapeutic effects in the experimental colitis.
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: p-hassanzadeh@razi.tums.ac.ir.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Hassanzadeh
authors.affiliation: Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Teheran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Arbabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Teheran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Teheran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D063388:Endocannabinoids / Q000008:administration & dosage* / Q000494:pharmacology; D005989:Glycerides / Q000008:administration & dosage* / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D037742:Nanotubes, Carbon; C094503:glyceryl 2-arachidonate; D014302:Trinitrobenzenesulfonic Acid
keywords: 2-arachidonoyglycerol; Carbon nanotubes; Colitis; Rat