title: Analysis of polyethylene-glycol-polylactide nano-dimension artificial red blood cells in maintaining systemic hemoglobin levels and prevention of methemoglobin formation.
abstract: 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.
authors.affiliation: Artificial Cells and Organs Research Centre, MSSS-FRSQ Research Group (equipe) on Blood Substitutes in Transfusion Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. artcell.med@mcgill.ca
authors.forename: Thomas M S
authors.initials: TM
authors.lastname: Chang
authors.forename: Douglas
authors.initials: D
authors.lastname: Powanda
authors.forename: W P
authors.initials: WP
authors.lastname: Yu
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry* / Q000494:pharmacology; D002214:Capsules / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D006454:Hemoglobins / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008706:Methemoglobin; D008970:Molecular Weight; D036103:Nanotechnology; D011091:Polyesters / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers; D051381:Rats
chemical_list: D001802:Blood Substitutes; D002214:Capsules; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D006454:Hemoglobins; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols; C083464:poly(ethyleneglycol-lactide); D008706:Methemoglobin