Analysis of Polyethylene-glycol-polylactide Nano-Dimension Artificial Red Blood Cells in Maintaining Systemic Hemoglobin Levels and Prevention of Methemoglobin Formation

We have recently reported our study on novel nano-dimension red blood cell (rbc) substitute based on ultrathin PEG-PLA membrane nanocapsules (80-150 nanometer diameter) containing hemoglobin (Hb) and enzymes. These have a markedly increased the circulation half-times as compared to our earlier PLA membrane nanocapsules. In the present study to be reported here, instead of looking at this from a pharmacodynamic point of view, we design the Hb nanocapsules from the point of view of transfusion medicine. For instance, the maximal levels of systemic non-red blood cell (rbc) Hb that can be attained after one infusion of 30% blood volume of 10 gm dl Hb in the form of different types of PEG-PLA Hb nanocapsules or polyHb. Also the length of time one infusion can maintain a given systemic non-rbc hemoglobin Hb level. Of the two types of polyhemoglobins similar to those in clinical trials but prepared in this laboratory, the maximal levels of Hb reached were 3.35 gm dl and 3.10 gm dl respectively. The times for the hemoglobin level to fall to 1.67 gm dl were 14 hours and 10. hours respectively, corresponding to 24 hours and 17 hours in human. The best PEG-PLA Hb nanocapsules are prepared using a combination of the following 4 factors: use of polymerized Hb, the use of higher M.W. PLA, the use of higher concentrations of PEG-PLA and the crosslinking of the newly formed PEG-PLA Hb nanocapsules. With this, the maximal non-rbc systemic Hb reached was 3.66 gm dl and the time to reach 1.67 gm dl was 24.2 hours, or 41.5 hours in human if extrapolated using the results obtained with polyHb in rats.