title: Polyethylene-glycolylated isoniazid conjugate for reduced toxicity and sustained release.
abstract: BACKGROUND
  The antitubercular drug, isoniazid (INH), has been conjugated with a bifunctional polyethylene glycol derivative (MW 575) with the objective of designing a novel drug-delivery system that has reduced toxicity compared with the neat drug, without compromising its biological activity. The polyethylene glycol-bis(INH) conjugate was synthesized in high yield and was completely characterized by infrared, NMR and mass spectroscopies.
  
  
  RESULTS
  This conjugate was labeled with a 99mTc radionuclide with less than 95% labeling efficiency. MTT assay revealed lower cytotoxicity of the conjugate compared with INH. Blood kinetics in rabbits and biodistribution in mice compared the blood retention of the drug and its polymer conjugate and their uptake in various organs, respectively. Biodistribution and gamma-scintigraphy in infection-induced animal models showed significantly high accumulation of the polymer-drug conjugate at the site of infection and retention for a long duration.
  
  
  CONCLUSIONS
  This conjugate could prove to be a good lead molecule for infection diagnosis and therapy.
authors: Division of Cyclotron & Radiopharmaceutical Sciences, Institute of Nuclear Medicine & Allied Sciences, Brig S K Mazumdar Road, Timarpur, Delhi-110054, India.
authors: Dipti
authors: D
authors: Kakkar
authors: Anjani K
authors: AK
authors: Tiwari
authors: Krishna
authors: K
authors: Chuttani
authors: Raj
authors: R
authors: Kumar
authors: Krishnanand
authors: K
authors: Mishra
authors: Harpal
authors: H
authors: Singh
authors: Anil K
authors: AK
authors: Mishra
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D007538:Isoniazid / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits
chemical_list: D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D011092:Polyethylene Glycols; D007538:Isoniazid