Garrido María Del Prado, Borreguero Ana Maria, Redondo Francisco Javier, Padilla David, Carmona Manuel, Ramos María Jesús, Rodriguez Juan Francisco
Department of Chemical Engineering, Institute of Chemical and Environmental Technology, University of Castilla-La Mancha, Avda. De Camilo José Cela 1, 13005 Ciudad Real, Spain.
Department of Anesthesiology and Critical Care Medicine, University General Hospital, Obispo Rafael Torija s/n, 13005 Ciudad Real, Spain.
Materials (Basel). 2022 Aug 30;15(17):5989. doi: 10.3390/ma15175989.
Hyperbilirubinemia is one of the main causes of death in patients with severe hepatic problems, which justifies the research for bilirubin removal solutions. In this study, St-MMA particles with PEGMA and/or GMA brushes were synthesized. First, the recipe for St-MMA was optimized and then adapted for PEGMA and GMA incorporation. Different solvents were then assayed to improve the BSA immobilization capacity of the particles. Ethyl lactate proved to be the best solvent, reaching a BSA immobilization capacity improvement of up to 60% for St-MMA-GMA-PEGMA particles. These particles also presented the best results for BR removal from PBS. No significant differences in the final capacity for BR removal from PBS media were observed when BSA was attached to the particles; however, the kinetics were greatly improved, requiring half the time. Finally, St-MMA-GMA-PEGMA particles that were wetted in EL with BSA reduced the bilirubin concentration in plasma from levels that threaten the survival of critical patients to levels close to those of healthy individuals in less than 30 min. On the contrary, particles without BSA were unable to remove bilirubin from plasma. Thus, the attachment of albumin to the particles plays a key role in selectively reducing bilirubin levels.
高胆红素血症是严重肝脏疾病患者主要死因之一，这使得胆红素清除解决方案的研究具有合理性。在本研究中，合成了带有聚乙二醇甲基丙烯酸酯（PEGMA）和/或甲基丙烯酸缩水甘油酯（GMA）刷的苯乙烯 - 甲基丙烯酸甲酯（St - MMA）颗粒。首先，优化了St - MMA的配方，然后调整配方以加入PEGMA和GMA。接着测定不同溶剂以提高颗粒固定牛血清白蛋白（BSA）的能力。结果表明乳酸乙酯是最佳溶剂，对于St - MMA - GMA - PEGMA颗粒，其固定BSA的能力提高了60%。这些颗粒在从磷酸盐缓冲盐水（PBS）中去除胆红素（BR）方面也呈现出最佳结果。当BSA附着在颗粒上时，在从PBS介质中去除BR的最终能力上未观察到显著差异；然而，动力学得到了极大改善，所需时间减半。最后，用BSA在乳酸乙酯中润湿的St - MMA - GMA - PEGMA颗粒在不到30分钟的时间内将血浆中的胆红素浓度从危及重症患者生存的水平降低到接近健康个体的水平。相反，没有BSA的颗粒无法从血浆中去除胆红素。因此，白蛋白附着在颗粒上在选择性降低胆红素水平方面起着关键作用。
