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壳聚糖接枝低分子量聚乳酸用于蛋白质包封和降低突释效应。

Chitosan grafted low molecular weight polylactic acid for protein encapsulation and burst effect reduction.

机构信息

Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Tr. T. Bati 5678, 760 01 Zlin, Czech Republic.

Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8, Prague 2 128 43, Czech Republic.

出版信息

Int J Pharm. 2015 Dec 30;496(2):912-21. doi: 10.1016/j.ijpharm.2015.10.017. Epub 2015 Oct 24.

Abstract

Chitosan and chitosan-grafted polylactic acid as a matrix for BSA encapsulation in a nanoparticle structure were prepared through a polyelectrolyte complexation method with dextran sulfate. Polylactic acid was synthetized via a polycondensation reaction using the non-metal-based initiator methanesulfonic acid and grafted to the chitosan backbone by a coupling reaction, with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as the condensing agent. The effect of concentration of the polymer matrix utilized herein on particle diameter, ζ-potential, encapsulation efficiency, and the release kinetic of the model protein bovine serum albumin at differing pH levels was investigated. The influence of pH and ionic strength on the behavior of the nanoparticles prepared was also researched. Results showed that grafting polylactic acid to chitosan chains reduced the initial burst effect in the kinetics of BSA release from the structure of the nanoparticles. Furthermore, a rise in encapsulation efficiency of the bovine serum albumin and diminishment in nanoparticle diameter were observed due to chitosan modification. The results suggest that both polymers actually show appreciable encapsulation efficiency; and release rate of BSA. CS-g-PLA is more suitable than unmodified CS as a carrier for controlled protein delivery.

摘要

壳聚糖和壳聚糖接枝聚乳酸作为一种基质,通过与硫酸葡聚糖的聚电解质复合方法制备用于 BSA 包封的纳米颗粒结构。聚乳酸通过使用非金属引发剂甲磺酸的缩聚反应合成,并通过偶联反应接枝到壳聚糖主链上,使用 1-乙基-3-(3-二甲基氨基丙基)碳二亚胺作为缩合剂。研究了所使用的聚合物基质的浓度对粒径、ζ-电位、包封效率以及在不同 pH 值下模型蛋白牛血清白蛋白的释放动力学的影响。还研究了 pH 值和离子强度对所制备的纳米颗粒行为的影响。结果表明,聚乳酸接枝到壳聚糖链上降低了纳米颗粒结构中 BSA 释放动力学的初始突释效应。此外,由于壳聚糖的修饰,观察到牛血清白蛋白的包封效率提高和纳米颗粒直径减小。结果表明,两种聚合物实际上都表现出相当高的包封效率和 BSA 的释放速率。CS-g-PLA 比未改性的 CS 更适合作为控制蛋白质递送的载体。

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