Analysis of polyethylene-glycol-polylactide nano-dimension artificial red blood cells in maintaining systemic hemoglobin levels and prevention of methemoglobin formation
Analysis of polyethylene-glycol-polylactide nano-dimension artificial red blood cells in maintaining systemic hemoglobin levels and prevention of methemoglobin formation
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DOI：
10.1081/bio-120023155
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发表时间：
2003-01-01
影响因子：
--
通讯作者：
Powanda, D
中科院分区：
文献类型：
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作者：
Chang, TMS;Powanda, D
我们最近报道了我们的研究，新型的纳米尺寸的红细胞（红细胞）替代品的基础上，PEG-PLA膜纳米胶囊（80-150纳米直径）含有血红蛋白（Hb）和酶。与我们早期的PLA膜纳米胶囊相比，这些纳米胶囊显着增加了循环半衰期。在这里报告的本研究中，我们不是从药效学的角度来看待这个问题，而是从输血医学的角度来设计Hb纳米胶囊。例如，在以不同类型的PEG-PLA Hb纳米胶囊或聚Hb的形式一次输注30%血液体积的10 gm/dl Hb后可以获得的全身非红细胞（rbc）Hb的最大水平。此外，一次输注的时间长度可以维持给定的全身非rbc血红蛋白Hb水平。在本实验室制备的与临床试验相似的两种多聚血红蛋白中，Hb的最高水平分别为3.35 gm/dl和3.10 gm/dl。血红蛋白水平降至1.67 gm/dl的时间分别为14小时和10小时。分别为24小时和17小时。最佳PEG-PLA Hb纳米胶囊的制备使用以下4个因素的组合：使用聚合的Hb，使用较高的M.W. PLA，使用更高浓度的PEG-PLA和交联新形成的PEG-PLA Hb纳米胶囊。由此，达到的最大非红细胞全身Hb为3.66 gm/dl，达到1.67 gm/dl的时间为24.2小时，如果使用大鼠中polyHb获得的结果外推，则人体为41.5小时。
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.