| The main goal of the research discussed in this dissertation is to create effective and safe cellular hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) for use in transfusion medicine. This dissertation focuses on the development and scale up production of cellular HBOCs composed of novel lipid formulations and polymers. The research concentrates on the development of cellular HBOCs over acellular HBOCs and abiotic O2 carriers, owing to their various advantages, such as, longer shelf-life, high Hb content, increased circulation half-life, biocompatibility, and absence of vasoactivity and hypertension in vivo.;This dissertation presents various novel large scale methods for the production of cellular HBOCs. The methods discussed are very efficient as HBOCs are produced with very reproducible biophysical properties. All the methods are designed with cost effectiveness in mind. The methods presented are simple and easily scalable to an industrial scale. In addition, they eliminate the use of energy consuming equipment/methods used in the production of other cellular HBOCs. Moreover, all the scale up methods are designed to satisfy important design criteria required to develop an effective O2 carrier, such as, high Hb content, suitable biophysical properties to ensure proper O2 delivery to tissues and organs and absence of any free Hb in the dispersions.;This dissertation also outlines detailed insights on the role of the intracellular diffusion barrier, as a result of Hb encapsulation, on binding/release of gaseous molecules to Hb. It emphasizes the importance of the cellular membrane and Hb encapsulation, as well as the pivotal role it plays in regulating O 2 delivery or consumption of nitric oxide (NO) by Hb in cellular HBOCs. In addition, the ex vivo experiments in rat arterial segments discussed in this dissertation provide for the correlation between O2 delivery and NO consumption to Hb-induced vasoconstriction by using exogenous and endogenous sources of NO. Overall, this dissertation presents novel cellular HBOCs with a potential of being safe and effective O2 carriers for use in transfusion medicine. |
