Nano-Biopolymers Research Laboratory, School of Chemical Engineering, College of Engineering, University of Tehran, PO Box: 11155-4563, Tehran, Iran.
Nano-Biopolymers Research Laboratory, School of Chemical Engineering, College of Engineering, University of Tehran, PO Box: 11155-4563, Tehran, Iran.
J Pharm Sci. 2017 Dec;106(12):3623-3630. doi: 10.1016/j.xphs.2017.08.001. Epub 2017 Aug 18.
The objective of this work was to prepare the streptokinase (SK) entrapped in chitosan nanoparticles (CS NPs) using bulk mixing (BM) and microfluidic (MF) techniques. The physicochemical properties of the samples were characterized by means of scanning electron microscopy and dynamic light scattering analysis for optimizing CS and SK solution concentrations as well as pH values. The obtained results showed that CS NPs fabricated using MF chip have the most uniform morphology, spherical shape, and average diameter of 67 ± 13 nm along with a narrow polydispersity. Conversely, the NP samples prepared via BM method have an irregular and disordered morphology as well as a broad distribution in their particle size (452 ± 300 nm). The in vitro drug release from microfluidically generated CS NPs depicted the controlled release of SK without plateau regime compared to those samples prepared using BM method during 48 h. Also, the drug release kinetic followed Higuchi model which revealed that the Fickian diffusion was the predominant mechanism. Subsequently, in in vivo animal model test, the performance of SK in blood plasma exhibited higher amidolytic activity for SK entrapped in CS NP samples fabricated via MF technique compared to those NPs prepared using BM and also SK alone.
本工作旨在使用批量混合（BM）和微流控（MF）技术将链激酶（SK）包封于壳聚糖纳米颗粒（CS NPs）中。通过扫描电子显微镜和动态光散射分析对样品的物理化学性质进行了表征，以优化 CS 和 SK 溶液浓度以及 pH 值。结果表明，使用 MF 芯片制备的 CS NPs 具有最均匀的形态、球形形状和平均直径为 67±13nm 以及较窄的多分散性。相反，通过 BM 方法制备的 NP 样品具有不规则和无序的形态以及粒径分布较宽（452±300nm）。与通过 BM 方法制备的样品相比，微流化生成的 CS NPs 体外药物释放显示 SK 的控制释放，没有平台期，在 48 小时内。此外，药物释放动力学遵循 Higuchi 模型，表明菲克扩散是主要机制。随后，在体内动物模型试验中，SK 在血浆中的性能表现出更高的 amidolytic 活性，对于通过 MF 技术制备的 CS NP 样品中包封的 SK 与通过 BM 制备的那些 NPs 以及 SK 本身相比。
