Cationic cellulose nanocrystals for fast, efficient and selective heparin recovery

Heparin is one of the most important anticoagulant agents used in clinical applications. Commercial heparin production includes an isolation from mucosa and an additional enrichment step by cationic resins. However, this process remains time-consuming while heparin is obtained in very low concentrations with the presence of macromolecular impurities, such as proteins. Therefore, an alternative with a fast, efficient and selective heparin-recovery performance is highly desirable. In this work, we utilized a biomass-derived cellulose nanocrystal colloid conjugated with cationic polyelectrolytes for heparin recovery. The high specific surface area and brush-like structure significantly increased the heparin-capture speed and efficiency under physiologically relevant conditions, which were demonstrated by the methylene blue binding assay and quartz crystal microbalance measurement. We also found that a selective heparin capture can be realized via adjusting salt concentration or pH. Finally, we showed that after several recycle rounds, the heparin-recovery ability of the cationic nanocrystals was largely retained and the majority of active heparin dose was recovered, showing a significantly higher heparin-recovery performance than the commercial Amberlite IRA-900 and demonstrating its applicability from an economic perspective. Therefore, the reported cellulose nanocrystal-polymer conjugate represents a promising candidate for a green and efficient heparin recovery.