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自组装S多糖纳米颗粒与牛血清白蛋白的相互作用及其载多西他赛纳米颗粒的生物分布

Interactions of Self-Assembled S Polysaccharide Nanoparticles with Bovine Serum Albumin and Biodistribution of Its Docetaxel-Loaded Nanoparticles.

作者信息

Zhang Guangyuan, Qiao Jin, Liu Xin, Liu Yuran, Wu Ji, Huang Long, Ji Danyang, Guan Qingxiang

机构信息

Department of Pharmaceutics, School of Pharmacy, Jilin University, Changchun 130012, China.

出版信息

Pharmaceutics. 2019 Jan 19;11(1):43. doi: 10.3390/pharmaceutics11010043.

Abstract

Amphiphilic copolymers of stearic acid (SA)-modified s polysaccharides (BSPs-SA) with three different degrees of substitution (DSs) were synthesized. The effects of DS values on the properties of BSPs-SA nanoparticles were evaluated. Drug state, cytotoxicity, and histological studies were carried out. The affinity ability of bovine serum albumin (BSA) and the BSPs-SA nanoparticles was also characterized utilizing ultraviolet and fluorescence spectroscopy. Besides, the bioavailability and tissue distribution of docetaxel (DTX)-loaded BSPs-SA nanoparticles were also assessed. The results demonstrated that the DS increase of the hydrophobic stearic acid segment increased the negative charge, encapsulation efficiency, and drug-loading capacity while decreasing the critical aggregation concentration value as well as the release rate of docetaxel from the nanoparticles. Docetaxel was encapsulated in nanoparticles at the small molecules or had an amorphous status. The inhibitory capability of DTX-loaded BSPs-SA nanoparticles against 4T1 tumor cells was superior to that of Duopafei. The ultraviolet and fluorescence results exhibited a strong binding affinity between BSPs-SA nanoparticles and bovine serum albumin, but the conformation of bovine serum albumin was not altered. Additionally, the area under the concentration⁻time curve (AUC₀) of DTX-loaded BSPs-SA nanoparticles was about 1.42-fold higher compared with Duopafei in tumor-bearing mice. Docetaxel levels of DTX-loaded BSPs-SA nanoparticles in some organs changed, and more docetaxel accumulated in the liver, spleen, and the tumor compared with Duopafei. The experimental results provided a theoretical guidance for further applications of BSPs-SA conjugates as nanocarriers for delivering anticancer drugs.

摘要

合成了具有三种不同取代度(DSs)的硬脂酸(SA)修饰的s多糖(BSPs-SA)两亲性共聚物。评估了DS值对BSPs-SA纳米颗粒性质的影响。进行了药物状态、细胞毒性和组织学研究。还利用紫外和荧光光谱对牛血清白蛋白(BSA)与BSPs-SA纳米颗粒的亲和能力进行了表征。此外,还评估了载多西他赛(DTX)的BSPs-SA纳米颗粒的生物利用度和组织分布。结果表明,疏水性硬脂酸链段的DS增加会增加负电荷、包封效率和载药量,同时降低临界聚集浓度值以及多西他赛从纳米颗粒中的释放速率。多西他赛以小分子形式包裹在纳米颗粒中或呈无定形状态。载DTX的BSPs-SA纳米颗粒对4T1肿瘤细胞的抑制能力优于多帕菲。紫外和荧光结果显示BSPs-SA纳米颗粒与牛血清白蛋白之间具有很强的结合亲和力,但牛血清白蛋白的构象未改变。此外,在荷瘤小鼠中,载DTX的BSPs-SA纳米颗粒的浓度⁻时间曲线下面积(AUC₀)比多帕菲高约1.42倍。载DTX的BSPs-SA纳米颗粒在某些器官中的多西他赛水平发生了变化,与多帕菲相比,更多的多西他赛在肝脏、脾脏和肿瘤中积累。实验结果为BSPs-SA共轭物作为抗癌药物递送纳米载体的进一步应用提供了理论指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5892/6358745/ef51b17e0a2b/pharmaceutics-11-00043-g001.jpg

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