Cationic chitosan derivative for heparin reversal - in vitro and in vivo studies in rats

Kamil K. Kamiński 1Barbara Lorkowska 2Justyna Ciejka 1Karolina Zazakowny 1Krzysztof Szczubiałka 1Maria Nowakowska 1Ryszard Korbut 2

1. Jagiellonian University, Faculty of Chemistry, Ingardena 3, Kraków 30-060, Poland
2. Jagiellonian University Medical College Chair of Pharmacology (UJCM), Grzegórzecka 16, Kraków 31-531, Poland

Abstract

Heparin is a widely used anticoagulant agent, which unfortunately may show some side effects, including hemorrhages, osteoporosis and thrombocytopenia. Moreover, the therapeutic dose of heparin varies significantly depending on the patient and therefore cases of overdose are frequent. At present, if necessary, heparin is neutralized using protamine sulfate. That drug, an exogenous protein, can cause an allergic reaction after administration. So, there is a need for an alternative system which would efficiently neutralize heparin, while not inducing allergic reaction.

Recently, we have developed cationic chitosan derivatives in reaction with glycidyltrimethylammonium chloride [1] which have been shown to bind heparin efficiently in buffer solution and in human blood plasma.

In a current presentation we would like to show the preliminary results of in vitro and in vivo studies of chitosan derivative (ChGl2) as a heparin antidote using Wistar rat model. Effect of GhGl2 on heparin activity in animal blood was determined using aPTT (activated Partial Thromboplastin Time) tests. Our study revealed that in rat blood in vitro ChGl2 can neutralize anticoagulant activity of heparin as revealed by significant aPTT reduction. The dose of ChGl2 required for heparin neutralization was determined. Also, comparative in vitro studies on protamine interaction with heparin in animal blood were carried out.

During in vivo experiments, defined dose of heparin was injected into femoral vein of the animal. Than, a fixed dose (predetermined in in vitro tests) of ChGl2 was intravenously administrated to the animal. Blood samples were collected from the carotid artery at regular intervals and aPTT values in obtained samples were determined. The decrease aPTT levels followed the pattern observed in control experiments in which the protamine sulfate was used as an heparin reversal agent. The studies were completed by the ChGl2 toxicity tests.

Based on the experiments described above it was concluded that chitosan derivative (ChGl2) functions as an efficient heparin antidote in rats. The dose of ChGl2 required to bring down the heparin level in rat model is comparable to that of protamine. Further studies on larger population of animals are necessary to confirm the above conclusions and to bring the chitosan derivatives to the clinical studies.

 References.

1.  K. Kamiński, K. Zazakowny, K. Szczubialka, M. Nowakowska, pH-Sensitive Genipin-Cross-Linked Chitosan Microspheres For Heparin Removal Biomacromolecules 2008, 9, 3127–3132

Acknowledgements.  Project operated within the Foundation for Polish Science Team Programme (PolyMed, TEAM/2008-2/6) and Ventures Programme co-financed by the EU European Regional Development Fund. Project partially financed by a grant from Polish Ministry of Science and Higher education No. N N204 151336.

Legal notice
  • Legal notice:

    Copyright (c) Pielaszek Research, all rights reserved.
    The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
    In every case, proper references including Author(s) name(s) and URL of this webpage: http://science24.com/paper/22792 must be provided.

 

Related papers
  1. Nano/micro drug carriers
  2. Studies on the inhibition mechanism of the human coronavirus NL63 replication by polycations
  3. Polisacharydowo-białkowe membrany do rekonstrukcji rogówki
  4. Protoporphyrine IX and its PEI derivatives as possible photosensitizer in antibacterial photodynamic therapy
  5. Albumin-HMchitosanGTMAC-based nanoparticles as potential controlled release delivery systems of curcumin
  6. Novel nanostructural photosensitizers for photodynamic therapy
  7. Selective adsorbents of adenosine-5'-triphosphate
  8. Novel polymeric inhibitors of human coronavirus NL63
  9. Superparamagnetyczne nanocząstki tlenku żelaza opłaszczane pochodnymi chitozanu – nowe kontrasty do MRI
  10. Polymeric Nanocapsules for Controlled Delivery of Lipophilic Drugs
  11. Dextran-based materials reducing anticoagulant activity of heparin in animal models in vitro and in vivo
  12. Preliminary studies on a new way of nucleic acids extraction using hydrogel microsphere
  13. Properties of DODAB/oleyl alcohol and DODAB/cholesterol monolayers and bilayers
  14. Synthesis and physicochemical properties of cationic chitosan derivative for heparin complexation

Presentation: Oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Kamil K. Kamiński
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-02-24 21:40
Revised:   2010-03-04 13:53
Google
 
Web science24.com
© 1998-2021 pielaszek research, all rights reserved Powered by the Conference Engine