Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Development a Novel Nano-Platform for Thrombolysis Acceleration by Thrombin Sensitive Polymer-Peptide Hybrid Nancapsules Publisher Pubmed



Farnoudianhabibi A1, 2 ; Aliebrahimi S3 ; Sehati F4 ; Nabavizadeh F5 ; Asadi H6 ; Montazeri V3 ; Van Nostrum CF7 ; Radmalekshahi M1 ; Nasser Ostad S8
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Nano-Encapsulation in the Food, Nutraceutical, and Pharmaceutical Industries Group (NFNPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  3. 3. Department of Artificial Intelligence, Smart University of Medical Sciences, Tehran, Iran
  4. 4. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Physiology, Tehran University of Medical Sciences and Health Services, Tehran, Iran
  6. 6. Polymer Laboratory, Chemistry Department, School of Science, University of Tehran, Tehran, Iran
  7. 7. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
  8. 8. Toxicology and Poisoning Research Center, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Pharmaceutics Published:2024


Abstract

According to the importance of time in treatment of thrombosis disorders, faster than current treatments are required. For the first time, this research discloses a novel strategy for rapid dissolution of blood clots by encapsulation of a fibrinolytic (Reteplase) into a Thrombin sensitive shell formed by polymerization of acrylamide monomers and bisacryloylated peptide as crosslinker. Degradability of the peptide units in exposure to Thrombin, creates the Thrombin-sensitive Reteplase nanocapsules (TSRNPs) as a triggered release system. Accelerated thrombolysis was achieved by combining three approaches including: deep penetration of TSRNPs into the blood clots, changing the clot dissolution mechanism by altering the distribution pattern of TSRNPs to 3D intra-clot distribution (based on the distributed intra-clot thrombolysis (DIT) model) instead of peripheral and unidirectional distribution of unencapsulated fibrinolytics and, enzyme-stimulated release of the fibrinolytic. Ex-vivo study was carried out by an occluded tube model that mimics in-vivo brain stroke as an emergency situation where faster treatment in short time is a golden key. In in vivo, efficacy of the developed formulation was confirmed by PET scan and laser Doppler flowmetry (LDF). As the most important achievements, 40.0 ± 0.7 (n = 3) % and 37.0 ± 0.4 (n = 3) % reduction in the thrombolysis time (faster reperfusion) were observed by ex-vivo and in-vivo experiments, respectively. Higher blood flow and larger digestion mass of clot at similar times in comparison to non-encapsulated Reteplase were observed that means more effective thrombolysis by the developed strategy. © 2024
Related Docs
1. Enhanced Thrombolysis Using Tissue Plasminogen Activator (Tpa)-Loaded Pegylated Plga Nanoparticles for Ischemic Stroke, Journal of Drug Delivery Science and Technology (2019)