Synthesis and Physicochemical Characterization of a Series of Hemoglobin-Based Oxygen Carriers: Objective Comparison between Cellular and Acellular Types
| Autor: | Hiroto Onuma, Shinji Takeoka, Eishun Tsuchida, Hiromi Sakai, Minako Yuasa |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Erythrocyte Aggregation
Oncotic pressure Rouleaux Erythrocytes Biomedical Engineering Pharmaceutical Science Bioengineering Nanotechnology Polyethylene Glycols Microcirculation Hydroxyethyl Starch Derivatives Hemoglobins Blood Substitutes Osmotic Pressure medicine Humans Osmotic pressure Colloids Particle Size Pharmacology Viscosity Chemistry Organic Chemistry Human serum albumin Molecular Weight Oxygen Membrane Glutaral Permeability (electromagnetism) Biophysics Hemoglobin Biotechnology medicine.drug |
| Zdroj: | Bioconjugate Chemistry. 11:56-64 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc9900789 |
| Popis: | A series of hemoglobin (Hb)-based O(2) carriers, acellular and cellular types, were synthesized and their physicochemical characteristics were compared. The acellular type includes intramolecularly cross-linked Hb (XLHb), polyoxyethylene (POE)-conjugated pyridoxalated Hb (POE-PLP-Hb), hydroxyethylstarch-conjugated Hb (HES-XLHb), and glutaraldehyde-polymerized XLHb (Poly-XLHb). The cellular type is Hb-vesicles (HbV) of which the surface is modified with POE (POE-HbV). Their particle diameters are 7 +/- 2, 22 +/- 2, 47 +/- 17, 68 +/- 24, and 224 +/- 76 nm, respectively, thus all the materials penetrate across membrane filters with 0.4 microm pore size, though only the POE-HbV cannot penetrate across the filter with 0.2 microm pore size. These characteristics of permeability are important to consider an optimal particle size in microcirculation in vivo. POE-PLP-Hb ([Hb] = 5 g/dL) showed viscosity of 6.1 cP at 332 s(-1) and colloid osmotic pressure (COP) of 70.2 Torr, which are beyond the physiological conditions (human blood, viscosity = 3-4 cP, COP = ca. 25 Torr). XLHb and Poly-XLHb showed viscosities of 1.0 and 1.5 cp, respectively, which are significantly lower than that of blood. COP of POE-HbV is regulated to 20 Torr in 5% human serum albumin (HSA). HES-XLHb and POE-HbV/HSA showed comparable viscosity with human blood. Microscopic observation of human red blood cells (RBC) after mixing blood with POE-PLP-Hb or HES-XLHb disclosed aggregates of RBC, a kind of sludge, indicating a strong interaction with RBC, which is anticipated to modify peripheral blood flow in vivo. On the other hand, XLHb and POE-HbV showed no rouleaux or aggregates of RBC. The acellular Hbs (P(50) = 14-32 Torr) have their specific O(2) affinities determined by their structures, while that of the cellular POE-HbV is regulated by coencapsulating an appropriate amount of an allosteric effector (e.g., P(50) = 18, 32 Torr). These differences in physicochemical characteristics between the acellular and cellular types indicate the advantages of the cellular type from the physiological points of view. |
| Databáze: | OpenAIRE |
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