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具有改善溶解性特性的白蛋白-生物聚合物生物共轭物的优化与开发

Optimization and Development of Albumin-Biopolymer Bioconjugates with Solubility-Improving Properties.

作者信息

Pápay Zsófia Edit, Magramane Sabrina, Király Márton, Szalkai Petra, Ludányi Krisztina, Horváth Péter, Antal István

机构信息

Department of Pharmaceutics, Semmelweis University, H-1092 Budapest, Hungary.

Department of Pharmaceutical Chemistry, Semmelweis University, H-1092 Budapest, Hungary.

出版信息

Biomedicines. 2021 Jun 26;9(7):737. doi: 10.3390/biomedicines9070737.

Abstract

Bioconjugation is an emerging field in the food and pharmaceutical industry. Due to its biocompatibility and high ligand binding capacity, albumin is widely used in modern drug delivery systems. However, the protein is sensitive to environmental stresses; albumin conjugates, on the other hand, have improved functional properties. Biopolymers are gaining interest due to their biodegradability and safety, compared to synthetic polymers. In this study, albumin-biopolymer bioconjugates were prepared by nonenzymatic Maillard reaction at 60 °C and 80% relative humidity. This nonenzymatic conjugation takes place between reducing sugars and available amino groups of a protein in certain conditions. The optimal molar ratio and time for the conjugation were studied by several investigation methods, including circular dichroism and fluorescence spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and determination of available amino groups with ortho-phthaldialdehyde (OPA) assay. All of the measurements provided evidence for the covalent bonding of albumin and biopolymers, resulting in bioconjugates. Based on the results, a higher molar ratio and longer time are necessary to complete the reaction with the available amino groups. However, the optimal parameters are specific to each given biopolymer. The rheological behavior of the conjugates is characteristic of the initial biopolymer, which can be useful in drug development. Moreover, both the physical characteristics of albumin and the solubility-improving capacity were enhanced. Therefore, the potential use of albumin-biopolymer bioconjugates in the pharmaceutical industry could be considered.

摘要

生物共轭是食品和制药行业中一个新兴的领域。由于其生物相容性和高配体结合能力,白蛋白在现代药物递送系统中被广泛应用。然而,这种蛋白质对环境压力敏感;另一方面,白蛋白共轭物具有改善的功能特性。与合成聚合物相比,生物聚合物因其生物可降解性和安全性而受到关注。在本研究中,通过在60°C和80%相对湿度下的非酶美拉德反应制备了白蛋白-生物聚合物共轭物。这种非酶共轭在特定条件下发生在还原糖和蛋白质的可用氨基之间。通过多种研究方法,包括圆二色性和荧光光谱、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)以及用邻苯二甲醛(OPA)测定法测定可用氨基,研究了共轭的最佳摩尔比和时间。所有测量结果都为白蛋白和生物聚合物的共价键合提供了证据,从而形成了共轭物。根据结果,需要更高的摩尔比和更长的时间来与可用氨基完成反应。然而,最佳参数因每种给定的生物聚合物而异。共轭物的流变行为是初始生物聚合物的特征,这在药物开发中可能有用。此外,白蛋白的物理特性和改善溶解性的能力都得到了增强。因此,可以考虑白蛋白-生物聚合物共轭物在制药行业的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50ab/8301381/2f49ab9646a0/biomedicines-09-00737-g001.jpg

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