Pacheco Marisa O, Lutz Henry M, Armada Jostin, Davies Nickolas, Gerzenshtein Isabelle K, Cakley Alaura S, Spiess Bruce D, Stoppel Whitney L
Department of Chemical Engineering, University of Florida, Gainesville FL.
Department of Anesthesiology, College of Medicine, University of Florida, Gainesville FL.
Adv Nanobiomed Res. 2023 Sep;3(9). doi: 10.1002/anbr.202300019. Epub 2023 Jul 27.
Oxygen therapeutics have a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all-natural or semi-synthetic hemoglobin-based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products stalled in development due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers. This work leverages the properties of silk fibroin, a cytocompatible and non-thrombogenic biopolymer, known to entrap protein-based cargo, to engineer a fully protein-based oxygen carrier. Herein, an all-aqueous solvent evaporation technique was used to form silk particles via phase separation from a bulk polyvinyl alcohol phase (PVA). Particles size was tuned, and particles were formed with and without hemoglobin. The encapsulation efficiency and ferrous state of hemoglobin were analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 µg/mL active hemoglobin in certain sfHBOC formulations. The system did not elicit a strong inflammation response , demonstrating the potential for this particle system to serve as an injectable HBOC.
氧疗法在输血医学和疾病治疗中有一系列应用。合成分子以及全天然或半合成的基于血红蛋白的氧载体（HBOCs）作为潜在的循环氧载体已取得成功。然而，许多早期的HBOC产品由于血流中过量血红蛋白以及血红蛋白进入组织所产生的副作用而在研发中停滞不前。为克服这些问题，研究集中于通过聚合血红蛋白分子或将血红蛋白包裹于脂质体载体中来增加血红蛋白的分子直径。这项工作利用了丝素蛋白的特性，丝素蛋白是一种细胞相容性且无血栓形成性的生物聚合物，已知其能够包裹基于蛋白质的物质，以此来设计一种完全基于蛋白质的氧载体。在此，采用全水性溶剂蒸发技术通过从本体聚乙烯醇相（PVA）进行相分离来形成丝颗粒。对颗粒大小进行了调整，并在有和没有血红蛋白的情况下形成颗粒。分析了血红蛋白的包封效率和亚铁状态，得到60%的包封效率以及最高20%的高铁血红蛋白，在某些丝素蛋白基氧载体配方中产生了100μg/mL的活性血红蛋白。该系统未引发强烈的炎症反应，表明这种颗粒系统有潜力作为一种可注射的HBOC。
