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. CONCLUSION: This conjugate could prove to be a good lead molecule for infection diagnosis and therapy.