■由于物理化学的不稳定性,在具有高稳定性和新的药物递送系统(NDD)的溶液中配制人生长激素(hGH)是如此困难。这项研究的目的是研究使用Tris作为hGH稳定剂的可能性。
■在本实验研究中,三(羟甲基)氨基甲烷(Tris)的作用被评估为磷酸盐缓冲液中的hGH稳定剂,作为一种实用的水溶液和释放NDD的介质。采用高效液相色谱(HPLC)和酶联免疫吸附测定(ELISA)研究了hGH在溶液中的稳定性,并采用动态光散射(DLS)测量了Tris对hGH在水溶液中流体动力学大小的影响。使用紫外(UV)分光光度法检查hGH光谱。在计算研究中,Tris-hGH的配体-蛋白质复合物的形成,通过分子对接模型研究了Tris与hGH的分子间相互作用。
■结果表明,Tris在最佳浓度下,增加hGH在水溶液中的稳定性。此外,分子对接模型证实了酪氨酸(Tyr)等氨基酸残基,脯氨酸(Pro),谷氨酸(Glu),天冬氨酸(Asp),亮氨酸(Leu),和苯丙氨酸(Phe)在hGH结构,与Tris作为配体连接。
■似乎hGH与Tris之间的相互作用是hGH在含有Tris的水溶液中物理化学稳定性增加的最重要原因。
UNASSIGNED: It is so difficult to formulate human growth hormone (hGH) in a solution with high stability and new drug delivery system (NDDs) due to physiochemical instability. The purpose of this study was to investigate the possibility of using Tris as a hGH stabilizer.
UNASSIGNED: In this experimental study, the role of tris(hydroxymethyl)aminomethane (Tris) was evaluated as a hGH stabilizing agent in phosphate buffer, as a practical aqueous solution and a media to release NDDs. Highperformance liquid chromatography (HPLC) and enzyme-linked immune sorbent assay (ELISA) were applied to investigate the stability of hGH in solutions and dynamic light scattering (DLS) was used to measure the effect of Tris on the hydrodynamic size of hGH in aqueous solutions. Ultra violet (UV) spectrophotometry was used to check the hGH spectrum. In computational study, formation of ligand-protein complex of the Tris-hGH, and the intermolecular interactions between Tris and hGH were studied by molecular docking modeling.
UNASSIGNED: The results demonstrated that Tris at the optimum concentration, increases hGH stability in aqueous solutions. Also, molecular docking modeling confirmed that amino acid residues such as tyrosine (Tyr), proline (Pro), glutamic acid (Glu), aspartic acid (Asp), leucine (Leu), and phenylalanine (Phe) in hGH structure, were linked with Tris as a ligand.
UNASSIGNED: It seems that interactions between hGH and Tris are the most important reason for increment of the physicochemical stability of hGH in aqueous solutions containing Tris.