Highly Efficient Recovery of Heparin Using a Green and Low-Cost Quaternary Ammonium Functionalized Halloysite Nanotube

Heparin, a highly sulfated polysaccharide, has been widely utilized as a medical anticoagulant for more than 40 years. Nevertheless, it is challenging to obtain heparin at high concentrations in the presence of other types of macromolecules, such as proteins and nucleic acids typically present in biological samples, because of the very low concentration of heparin in starting materials. To solve this issue, we prepared (3-aminopropyl) triethoxysilane (3-APTES) functionalized halloysite nanotubes (HNTs) for efficient heparin capture. The prepared nanotubes were further quaternized using methyl iodide to improve the efficiency of heparin adsorption at alkaline conditions. The recovery of heparin improved with both the functionalization of the HNTs with 3-APTES and the quaternization of the ammonium groups to enable a strong polyelectrolyte character with a high positive charge density that was superior at recovering heparin compared to Amberlite FPA98 Cl, a common adsorbent widely utilized for heparin recovery. Zeta potential and X-ray photoelectron spectroscopy measurements confirmed that the −N(CH3)3+ groups onto the HNT–NR3+ had a great affinity to bind to the −SO4–2 groups of heparin because of the electrostatic interaction. The influences of experimental variables on heparin uptake efficiency of HNT–NR3+ were also studied, and the equilibrium results were evaluated by diverse isotherm and kinetic models. Moreover, successful regeneration of the HNT–NR3+ was proven using a saturated-NaCl solution, so that the heparin uptake procedure could be redone without significant loss in capacity of adsorption. Furthermore, HNT–NR3+ selectively adsorbed heparin from a biological mixture of heparin isolated from porcine intestinal mucosa. The prepared HNT–NR3+ was found to be a propitious candidate to be used as a green, inexpensive, and effective adsorbent for heparin separation.