1. Low-molecular-weight sulfonated chitosan as template for anticoagulant nanoparticles.
- Author
-
Heise K, Hobisch M, Sacarescu L, Maver U, Hobisch J, Reichelt T, Sega M, Fischer S, and Spirk S
- Subjects
- Anticoagulants chemistry, Chitosan chemistry, Humans, Metal Nanoparticles chemistry, Molecular Weight, Partial Thromboplastin Time, Prothrombin Time, Alkanesulfonates chemistry, Anticoagulants pharmacology, Chitosan pharmacology, Metal Nanoparticles administration & dosage, Silver chemistry
- Abstract
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., Results: In-depth characterization revealed a sulfoalkylation of chitosan mainly on its sterically favored O 6-position. Moreover, comparably high average degrees of substitution with sulfoethyl groups (DS
SE ) 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., Competing Interests: Disclosure The authors report no conflicts of interest in this work.- Published
- 2018
- Full Text
- View/download PDF