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Preparation of Peg-Grafted Chitosan/Streptokinase Nanoparticles to Improve Biological Half-Life and Reduce Immunogenicity of the Enzyme Publisher Pubmed



Baharifar H1 ; Khoobi M2 ; Arbabi Bidgoli S3 ; Amani A4, 5
Authors
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Authors Affiliations
  1. 1. Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
  2. 2. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Islamic Azad University, Tehran Medical Sciences (IAUTMS), Tehran, Iran
  4. 4. Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
  5. 5. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Biological Macromolecules Published:2020


Abstract

Streptokinase, as a thrombolytic drug, is widely used in treatment of cardiovascular disorders and deep vein thrombosis. Streptokinase is immunogenic due to its prokaryotic source, having short biological half-life (i.e. 15 to 30 min) that is not enough for an efficient therapy. In this study, nanoparticles (NPs) of chitosan/streptokinase and polyethylene glycol (PEG)-grafted chitosan/streptokinase were prepared by polyelectrolyte complex method. Particle size of chitosan and PEG-grafted chitosan NPs were 154 ± 42 and 211 ± 47 nm, respectively. Results showed that using PEG in preparation of nanoparticles leads to ~24% decrease in encapsulation efficiency. Encapsulation of streptokinase in the NPs also resulted in a slight reduction in enzymatic activity. However, in vivo findings indicated that response of the immune system was delayed for 20 days and blood circulation time of the enzyme increased up to 120 min by using PEG. Biological half-life of the drug also increased up to twice in PEG-grafted chitosan. In conclusion, PEG-grafted chitosan NPs could be an alternative for delivery of streptokinase to reduce its clinical limitations. © 2019