Applied Cellular Physiology and Metabolic Engineering

Encapsulation of hemoglobin inside liposomes surface conjugated with poly(ethylene glycol) attenuates their reactions with gaseous ligands and regulates nitric oxide dependent vasodilation

  1. Shahid Rameez1,
  2. Nicole Guzman1,
  3. Uddyalok Banerjee1,
  4. Jorge Fontes1,
  5. Michael E. Paulaitis1,
  6. Andre F. Palmer1,*,
  7. Rakesh P. Patel2,
  8. Jaideep Honavar2

Article first published online: 30 MAR 2012

DOI: 10.1002/btpr.1532

Issue

Biotechnology Progress

Biotechnology Progress

Volume 28, Issue 3, pages 636–645, May/June 2012

Additional Information

How to Cite

Rameez, S., Guzman, N., Banerjee, U., Fontes, J., Paulaitis, M. E., Palmer, A. F., Patel, R. P. and Honavar, J. (2012), Encapsulation of hemoglobin inside liposomes surface conjugated with poly(ethylene glycol) attenuates their reactions with gaseous ligands and regulates nitric oxide dependent vasodilation. Biotechnol Progress, 28: 636–645. doi: 10.1002/btpr.1532

Author Information

  1. 1

    William G. Lowrie Dept. of Chemical and Biomolecular Engineering, The Ohio State University, 425 Koffolt Laboratories, Columbus, OH 43210

  2. 2

    Dept. of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294

*William G. Lowrie Dept. of Chemical and Biomolecular Engineering, The Ohio State University, 425 Koffolt Laboratories, Columbus, OH 43210

Publication History

  1. Issue published online: 9 JUN 2012
  2. Article first published online: 30 MAR 2012
  3. Accepted manuscript online: 28 FEB 2012 08:35AM EST
  4. Manuscript Revised: 6 FEB 2012
  5. Manuscript Received: 24 OCT 2011

Funded by

  • National Institutes of Health. Grant Numbers: R01HL078840, R01DK070862, HL092624
  • National Science Foundation Nanoscience and Engineering Center in Affordable Nanoengineering of Polymer Biomedical Devices. Grant Number: EEC0914790

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Keywords:

  • liposomes;
  • hemoglobin;
  • oxygen

Abstract

Acellular hemoglobin (Hb)-based O2 carriers (HBOCs) are being investigated as red blood cell (RBC) substitutes for use in transfusion medicine. However, commercial acellular HBOCs elicit both vasoconstriction and systemic hypertension which hampers their clinical use. In this study, it is hypothesized that encapsulation of Hb inside the aqueous core of liposomes should regulate the rates of NO dioxygenation and O2 release, which should in turn regulate its vasoactivity. To test this hypothesis, poly(ethylene glycol) (PEG) conjugated liposome-encapsulated Hb (PEG-LEHs) dispersions were prepared using human and bovine Hb. In this study, the rate constants for O2 dissociation, CO association, and NO dioxygenation were measured for free Hb and PEG-LEH dispersions using stopped-flow UV–visible spectroscopy, while vasoactivity was assessed in rat aortic ring strips using both endogenous and exogenous sources of NO. It was observed that PEG-LEH dispersions had lower O2 release and NO dioxygenation rate constants compared with acellular Hbs. However, no difference was observed in the CO association rate constants between free Hb and PEG-LEH dispersions. Furthermore, it was observed that Hb encapsulation inside vesicles prevented Hb dependent inhibition of NO-mediated vasodilation. In addition, the magnitude of the vasoconstrictive effects of Hb and PEG-LEH dispersions correlated with their respective rates of NO dioxygenation and O2 release. Overall, this study emphasizes the pivotal role Hb encapsulation plays in regulating gaseous ligand binding/release kinetics and the vasoactivity of Hb. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012

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