Low-molecular-weight sulfonated chitosan as template for anticoagulant nanoparticles

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Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Date
2018-01-01
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Mcode
Degree programme
Language
en
Pages
14
4881-4894
Series
International journal of nanomedicine, Volume 13
Abstract
Results: In-depth characterization revealed a sulfoalkylation of chitosan mainly on its sterically favored O6-position. Moreover, comparably high average degrees of substitution with sulfoethyl groups (DSSE) of up to 1.05 were realized in reactions with NaBES. The harsh reaction conditions led to significant chain degradation and consequently, SECS exhibits masses of <50 kDa. Throughout the following microwave reaction, stable nanoparticles were obtained only from highly substituted products because they provide a sufficient charge density that prevented particles from aggregation. High-resolution transmission electron microscopy images reveal that the silver core (diameter ~8 nm) is surrounded by a 1-2 nm thick SECS layer. These core-shell particles and the SECS itself exhibit an inhibiting activity, especially on cofactor Xa. Conclusion: This interesting model system enabled the investigation of structure-property correlations in the course of nanoparticle formation and anticoagulant activity of SECS and may lead to completely new anticoagulants on the basis of chitosan-capped nanoparticles. Purpose: In this work, low-molecular-weight sulfoethyl chitosan (SECS) was used as a model template for the generation of silver core-shell nanoparticles with high potential as anticoagulants for medical applications. Materials and methods: SECS were synthesized by two reaction pathways, namely Michael addition and a nucleophilic substitution with sodium vinylsulfonate or sodium 2-bromoethanesulfonate (NaBES). Subsequently, these derivatives were used as reducing and capping agents for silver nanoparticles in a microwave-assisted reaction. The formed silver-chitosan core-shell particles were further surveyed in terms of their anticoagulant action by different coagulation assays focusing on the inhibition of either thrombin or cofactor Xa.
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Keywords
antithrombotic activity, chitosan ethylsulfonate, cofactor Xa, silver nanoparticles
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Citation
Heise, K, Hobisch, M, Sacarescu, L, Maver, U, Hobisch, J, Reichelt, T, Sega, M, Fischer, S & Spirk, S 2018, ' Low-molecular-weight sulfonated chitosan as template for anticoagulant nanoparticles ', International journal of nanomedicine, vol. 13, pp. 4881-4894 . https://doi.org/10.2147/IJN.S172230