Synthesis and physicochemical properties of cationic chitosan derivative for heparin complexation

Justyna Ciejka 1Kamil K. Kamiński 1Karolina Zazakowny 1Krzysztof Szczubiałka 1Maria Nowakowska 1Radosław Lach 2

1. Jagiellonian University, Faculty of Chemistry, Ingardena 3, Kraków 30-060, Poland
2. AGH University of Science and Technology, Department of Advanced Ceramics, Faculty of Materials Science and Ceramics (AGH), al. Mickiewicza 30, Kraków 30-059, Poland

Abstract

Chitosan is a biocompatible and biodegradable linear polysaccharide of great potential for biomedical applications[1]. We have found that chitosan can form complexes with heparin, an anionic polysaccharide commonly used as an anticoagulant drug.[2] Therefore it may be potentially useful as an agent for  neutralization an anticoagulant action of heparin.

         However, our model laboratory studies have shown that the efficiency of complexation  of unfractionated heparin (UFH) by pristine chitosan is low at the pH values characteristic for  blood (pH = 7.4). Therefore we have  modified chitosan to  obtain its cationic derivative  (ChGl).  That polymer is very well soluble in water  at pH 7.4. The interactions between cationically modified chitosan and heparin (both unfractionated and low-molecular-weight one (LMWH)) have been studied. It was shown that heparin complexation capability by ChGl is comparable to that of protamine sulfate, currently  used as a drug of choice for heparin neutralization. Both complexes (ChGl-UFH and ChGl-LMWH) are stable at neutral pH. What is more the thermal sterilization of cationic chitosan (at 1600C for 1 hour) does not influence its capability of heparin binding.

Using dynamic light scattering (DLS) technique we have  determined the dimensions of the objects formed as a result of complexation of UFH with PS and ChGl in the aqueous solutions (PBS buffer, pH = 7.4). It has been found that  UFH-ChGl complexes have smaller dimensions  and lower  polydispersity than these formed as a results of heparin complexation with protamine ( UFH-PS).

References.

1. C. Shi, Y. Zhu, X. Ran, M. Wang, Y. Su, T. Cheng Therapeutic Potential of Chitosan and Its Derivatives in Regenerative Medicine Journal of Surgical Research 2006, 133,   185–192

2. 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.

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

Submitted: 2010-02-25 18:28
Revised:   2010-03-04 13:51
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