title: Novel approach for optimizing the capacity and efficacy of a protamine filter for clinical extracorporeal heparin removal.
abstract: The authors previously reported the development of a blood filter device containing immobilized protamine (termed "protamine filter") that could be used at the conclusion of an extracorporeal blood procedure to prevent heparin and protamine induced complications. In vitro and in vivo experiments have fully demonstrated the feasibility and utility of the approach. The bottleneck limitations of this approach, however, lie in the lack of efficacy and capacity of the filter device. In this article, the authors describe a method to improve the efficacy in heparin adsorption, by incorporating a poly(ethylene glycol) spacer arm between the immobilized protamine and the fiber surface to enhance its freedom to dynamic motion. The authors also describe a method to increase the capacity of the filter, by using a poly-L-lysine based amplification method to augment protamine loading on the fiber, and to create multiple layers of immobilized protamine for heparin adsorption. Results show that with a poly(ethylene glycol) spacer arm of 3,400 Da, heparin adsorption on the protamine-poly(ethylene glycol) fibers was increased dramatically from a value of 9.1 mg heparin per gram of fibers in the control (i.e., without the poly[ethylene glycol] spacer) to 60 mg heparin/g fiber. The use of the amplification method with 110 kDa poly-L-lysine also yielded a threefold increase in protamine loading, and, consequently, an approximately fourfold enhancement in heparin adsorption (from 9.1 to 38.0 mg heparin/g fiber). A combination of these two methods would yield an optimized protamine filter that could meet all types of clinical needs in heparin removal. As assessed from the in vivo theoretical model reported previously for the protamine filter, a 95% heparin removal under cardiopulmonary bypass conditions could be achieved with a single optimized protamine filter with a size smaller than a hemodialyzer cartridge.
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: V K
authors.initials: VK
authors.lastname: Singh
authors.forename: V C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D006440:Hemofiltration / Q000379:methods*; D006493:Heparin / Q000302:isolation & purification*; D006801:Humans; D011479:Protamines
chemical_list: D011479:Protamines; D006493:Heparin