A nontoxic disulfide bond reducing method for lipophilic drug-loaded albumin nanoparticle preparation: Formation dynamics, influencing factors and formation mechanisms investigation
A nontoxic disulfide bond reducing method for lipophilic drug-loaded albumin nanoparticle preparation: Formation dynamics, influencing factors and formation mechanisms investigation
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DOI：
10.1016/j.ijpharm.2012.12.035
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发表时间：
2013-02-25
影响因子：
5.8
通讯作者：
Liu, Jianping
中科院分区：
文献类型：
--
作者：
Jiang, Liqun;Xu, Yisheng;Liu, Jianping
本研究的目的是建立一种新的制备亲脂性载药白蛋白纳米粒的无毒二硫键还原方法，并对该方法进行系统的研究。半胱氨酸(Cys)被用来破坏白蛋白的二硫键，并引入药物与白蛋白的自组装。选择紫杉醇(PTX)和牛血清白蛋白(BSA)作为亲脂药物和白蛋白模型。通过测定颗粒的大小和产率等特性，研究了颗粒形成的动力学、影响因素和形成机理。成功制备了粒径为50~400 nm的纳米粒，载药率高达18.3%。PH值7-8是制备纳米粒子的适宜条件。温度、牛血清白蛋白浓度和半胱氨酸浓度对颗粒大小和产率有正向影响。当PTX的加入量小于PTX与牛血清白蛋白结合的最大量时，可以形成球形结构的粒子；否则，可以形成具有核壳结构的纳米粒子。这种新的无毒的二硫键还原方法为制备各种白蛋白基纳米载体提供了一种通用且安全的方法，可用于从药物(特别是亲脂性药物)的输送到疾病诊断的广泛应用。(C)2013爱思唯尔B.V.保留所有权利。
The purpose of this study was to establish a novel nontoxic disulfide bond reducing method for lipophilic drug-loaded albumin nanoparticle preparation and make a systematic investigation on this method. Cysteine (Cys) was used to break the disulfide bond of albumin and introduce the self-assembly of drug and albumin. Paclitaxel (PTX) and bovine serum albumin (BSA) were selected to be the model lipophilic drug and albumin. The particle formation dynamics, influencing factors and formation mechanisms were investigated by determining the characteristics of particles including the particle size and yield. Nanoparticles with diameter of 50-400 nm and drug loading efficiency up to 18.3% were prepared successfully. pH 7-8 was suitable for nanoparticle preparation. Temperature, BSA concentration and Cys concentration had positive effects on the particle size and yield. When PTX added was less than the maximal amount of PTX that could bind to BSA, particles with a spherical structure could be formed; otherwise nanoparticles with a core-shell structure could be formed. This novel nontoxic disulfide bond reducing method provides a common and safe method for preparing various kinds of albumin-based nanocarriers for a wide range of applications, from drug (especially the lipophilic drug) delivery to diagnosis of disease. (C) 2013 Elsevier B.V. All rights reserved.