Synthesis of Cross-Linked Spherical Polycationic Adsorbents for Enhanced Heparin Recovery.

Heparin, as an anticoagulant drug, is almost entirely produced via isolation from mucosal tissues of different animals; therefore, it is it is crucial to maximize its recovery. Adsorption of heparin from this complex biological mixture needs a specialized and highly effective adsorbent that almost separates only heparin from the mixture. In this work, a series of spherical cross-linked polymer bead adsorbents were synthesized via inverse suspension polymerization of water soluble monomers in corn oil, a benign solvent, and their performance for heparin adsorption from a biological sample of porcine mucosa was evaluated. To tune the performance and swelling of the resins, we varied the molar ratio of the monomer(s) to the cross-linker as well as the molar ratio of the monomers. The results of heparin recovery from biological porcine mucosa show that our optimized resin can outperform the commercially available resin in terms of adsorption efficiency of up to 18%. The adsorbed heparin was eluted, isolated, and its anticoagulant potency measured using the standard sheep plasma clotting assay. The isolated heparin samples were also analyzed by 1H NMR spectroscopy to check the possible impurities, and the results show the presence of chondroitin sulfate and dermatan sulfate, as is the case for the heparin eluted from the commercial resin. Furthermore, the effects of some experimental variables including the adsorbent dosage, pH, time, and recycling on heparin adsorption were studied, and the results show that these resins can be used for efficient recovery of heparin.