Preparation, characterization and in vivo investigation of blood-compatible hemoglobin-loaded nanoparticles as oxygen carriers

Although many attempts have been made to design advanced hemoglobin-based oxygen carriers (HBOCs), no clinically viable product has been widely approved, because they do not perform normal blood functions, such as coagulation, hematologic reactions and stability. Additionally, the in vivo oxygenation of hemoglobin-loaded nanoparticles (HbPs) encapsulated with polymers has seldom been proved. Herein, HbPs of approximately 200nm with good stability were successfully fabricated and exhibited oxygen-carrying capacity. The HbPs preserve the biological and structure features of hemoglobin according to UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectral analysis. In vitro, the HbPs showed a viscosity comparable to that of blood with no obvious effects on red blood cell aggregation. At the same time, blood compatibility was characterized in terms of platelet function, clot strength, speed of clot formation, degree of fibrin cross-linking and hemolysis rate. After intravenous administration of HbPs to mice with controlled hemorrhages, blood flow recovery and maintenance of systemic oxygenation were observed.