抗结核药物“异烟肼”固定白蛋白纳米颗粒的聚乙二醇化

Aldana Galiyeva, Y. Tazhbayev, Nazgul A. Yessentayeva, A.Т. Daribay, Dias T. Marsel, D. Sadyrbekov, L. Zhaparova, Zh.T. Arystanova
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摘要

聚乙二醇(PEG)被广泛应用于纳米医学,以延长药物在血液中的循环时间,提高药物疗效。通过将聚乙二醇连接到白蛋白大分子和纳米颗粒上是一种成熟的技术,称为聚乙二醇化。本研究的目的是制备和评估血清稳定的长循环peg -白蛋白异烟肼纳米颗粒用于治疗结核分枝杆菌,该纳米颗粒可以通过增加其渗透性,溶解度和在巨噬细胞中的积累来改善其治疗效果。首次以尿素和半胱氨酸为变性稳定剂,通过脱溶法制备了负载异烟肼的聚乙二醇化牛血清白蛋白纳米颗粒。通过改变聚乙二醇的浓度,获得了平均尺寸达300 nm的Na-noparticles。各粒子电荷的多分散性指数均小于0.1,表明粒径为单分散。ζ电位值表明纳米粒子具有足够的物理稳定性。SEM图像显示颗粒呈球形。TGA和DSC结果证实了载药不影响聚合物的结构。基于FT-IR研究,确定了聚乙二醇化BSA纳米颗粒与异烟肼之间不存在化学相互作用。在体外释放研究中,纳米颗粒被证明具有前兆释放。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PEGylation of Albumin Nanoparticles Immobilized with the Anti-Tuberculosis Drug “Isoniazid”
Polyethylene glycol (PEG) is widely used in nanomedicine to extend the circulation time of a drug in the blood and increase drug efficacy. Conjugation by attaching polyethylene glycol to an albumin macromolecule and nanoparticles is a well-established technique known as PEGylation. The aim of this research was to pre-pare and evaluate serum stable long circulating PEG-albumin-isoniazid nanoparticles for the treatment of Mycobacterium tuberculosis which can improve its therapeutic effect by increasing its permeability, solubili-ty and accumulation in aveolar macrophages. For the first time, PEGylated BSA nanoparticles loaded with isoniazid were synthesized by desolvation using urea and cysteine as denaturing and stabilizing agents. Na-noparticles with an average size of up to 300 nm were obtained by varying the PEG concentration. The polydispersity index of all particle charges was less than 0.1, indicating monodisperse size. The ζ potential values indicate sufficient physical stability of the nanoparticles. SEM images showed that the particles were spherical in shape. The TGA and DSC results obtained confirm that drug loading does not affect the structure of the polymer. Based on FT-IR studies, the absence of chemical interactions between PEGylated BSA nano-particles and isoniazid was established. In in vitro release studies, the nanoparticles were demonstrated to have a prologue release.
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