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Microencapsulation IV: Cross-linked hemoglobin microcapsules.

M C Lévy, P Rambourg, J Lévy

    Journal of Pharmaceutical Sciences
    |July 1, 1982
    PubMed
    Summary
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    Researchers developed stable hemoglobin microcapsules for oxygen delivery. These microcapsules, approximately 5 micrometers in diameter, maintain their oxygen-carrying properties even after lyophilization and rehydration.

    Area of Science:

    • Biomaterials Science
    • Chemical Engineering
    • Biotechnology

    Background:

    • Hemoglobin (Hb) is a potential oxygen carrier, but its clinical use is limited by instability and rapid clearance.
    • Developing safe and effective Hb-based oxygen carriers (HBOCs) is crucial for medical applications.

    Purpose of the Study:

    • To prepare stable hemoglobin microcapsules (HbMCs) with improved oxygen-carrying properties.
    • To optimize microencapsulation conditions for desirable characteristics like size, oxygen dissociation, and stability.
    • To evaluate the impact of lyophilization and rehydration on HbMC functionality.

    Main Methods:

    • Hemoglobin cross-linking using various acyldichlorides, with terephthaloylchloride identified as optimal.
    • Incorporation of inositol hexaphosphate and glucose to modulate oxygen affinity.

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  • Stabilization using glutaraldehyde and high stirring speed for controlled microcapsule formation (mean diameter ~5 µm).
  • Assessment of oxygen transfer properties (p50 = 13 mm Hg) and protease susceptibility.
  • Evaluation of properties post-lyophilization and rehydration.

    • Main Results:

    • Stable, 5-micrometer hemoglobin microcapsules were successfully prepared using terephthaloylchloride.
    • The microcapsules exhibited a sigmoidal oxygen dissociation curve with a p50 of 13 mm Hg, indicating efficient oxygen release.
    • While susceptible to protease lysis, the microcapsules retained their structural integrity and oxygen transfer capabilities after freeze-drying and rehydration.

    Conclusions:

    • Optimized cross-linking and stabilization methods yield functional hemoglobin microcapsules suitable for oxygen transport.
    • The developed HbMCs demonstrate promising oxygen-carrying capacity and stability, even after lyophilization, suggesting potential for storage and therapeutic use.
    • Further research into enhancing protease resistance could improve the in vivo applicability of these hemoglobin microcapsules.