Abstract

Hemoglobin (Hb)-based oxygen carriers (HBOCs) display the excellent oxygen-carrying properties of red blood cells, while overcoming some of the limitations of donor blood. Various encapsulation platforms have been explored to prepare HBOCs which aim to avoid or minimize the adverse effects caused by the administration of free Hb. Herein, we entrapped Hb within a poly(lactide-co-glycolide) (PLGA) core, prepared by the double emulsion solvent evaporation method. We study the effect of the concentrations of Hb, PLGA, and emulsifier on the size, polydispersity (PDI), loading capacity (LC), and entrapment efficiency (EE) of the resulting Hb-loaded PLGA nanoparticles (HbNPs). Next, the ability of the HbNPs to reversibly bind and release oxygen was thoroughly evaluated. When needed, trehalose, a well-known protein stabilizer that has never been explored for the fabrication of HBOCs, was incorporated to preserve Hb’s functionality. The optimized formulation had a size of 344 nm, a PDI of 0.172, a LC of 26.9%, and an EE of 40.7%. The HbNPs were imaged by microscopy and were further characterized by FTIR and CD spectroscopy to assess their chemical composition and structure. Finally, the ability of the encapsulated Hb to bind and release oxygen over several rounds was demonstrated, showing the preservation of its functionality.

Highlights

  • This is due to the fact that when they are too small, Hb-based oxygen carriers (HBOCs) can extravasate from the blood vessels into the subendothelial layer where they can act as scavengers of nitric oxide (NO), which is an important vasodilatory molecule

  • Very large HBOCs are a problem, since strong phagocytosis by the mononuclear phagocyte system occurs for particles in the micron range [16,17]

  • As the PLGA content was low when compared to Hb, and does not afford a significant chiral contribution, these results indicate that the average sample composition had a reduced helical structure with an increased β-sheet content

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The transfusion of donor blood, which usually consists of the administration of packed red blood cells (RBCs), is a widely used and essential procedure for saving lives and maintaining the normal physiological functions of our bodies [1,2]. While the medical demands for blood transfusions are high, donor blood is a scarce resource. As a result of the increasing population growth and aging, donor blood will become even more sparse in the upcoming years [3] the development of blood substitutes is an enduring and pressing need in biomedicine [4]

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