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用于基于蛋白质的药物递送系统的载牛血清白蛋白聚乳酸-羟基乙酸共聚物-壳聚糖复合纳米粒的合成与评价

Synthesis and Evaluation of BSA-Loaded PLGA-Chitosan Composite Nanoparticles for the Protein-Based Drug Delivery System.

作者信息

Gaur Manish, Maurya Sarita, Akhtar Mohd Sohail, Yadav Awadh Bihari

机构信息

Centre of Biotechnology, University of Allahabad, Prayagraj 211002, India.

Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.

出版信息

ACS Omega. 2023 May 17;8(21):18751-18759. doi: 10.1021/acsomega.3c00738. eCollection 2023 May 30.

Abstract

The purpose of this study was to synthesize composite nanoparticles (NPs) based on poly(d,l-lactic--glycolic acid) (PLGA) and chitosan (CS) and evaluate their suitability for the delivery of protein-based therapeutic molecules. Composite NPs possess a unique property which is not exhibited by any other polymer. Unlike other polymers, only the composite NPs lead to improved transfection efficiency and sustained release of protein. The composite NP were prepared by grafting CS on the surface of PLGA NPs through EDC-NHS coupling reaction. The size of bovine serum albumin (BSA)-loaded PLGA NPs and BSA-loaded PLGA-CS composite NPs was 288 ± 3 and 363 ± 4 nm, respectively. The zeta potential of PLGA NPs is -18 ± 0.23, and that of composite particles is 19 ± 0.40, thus confirming the successful addition of CS on the surface of PLGA NPs. Composite NPs were characterized using dynamic light scattering, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, release profile, and gel electrophoresis. The encapsulation efficiency of PLGA NPs was 88%. These composite NPs were easily uptaken by the A549 cell line with no or minimal cytotoxicity. The present study emphasizes that the composite NPs are suitable for delivery of BSA into the cells with no cytotoxicity or very little cytotoxicity, while maintaining the integrity of the encapsulated BSA.

摘要

本研究的目的是合成基于聚(d,l-乳酸-乙醇酸)(PLGA)和壳聚糖(CS)的复合纳米颗粒(NPs),并评估它们用于递送基于蛋白质的治疗性分子的适用性。复合纳米颗粒具有一种独特的性质,这是其他任何聚合物都不具备的。与其他聚合物不同,只有复合纳米颗粒能提高转染效率并实现蛋白质的持续释放。通过EDC-NHS偶联反应将CS接枝到PLGA纳米颗粒表面制备复合纳米颗粒。负载牛血清白蛋白(BSA)的PLGA纳米颗粒和负载BSA的PLGA-CS复合纳米颗粒的尺寸分别为288±3和363±4nm。PLGA纳米颗粒的zeta电位为-18±0.23,复合颗粒的zeta电位为19±0.40,从而证实CS成功添加到了PLGA纳米颗粒表面。使用动态光散射、扫描/透射电子显微镜、傅里叶变换红外光谱、X射线衍射、释放曲线和凝胶电泳对复合纳米颗粒进行了表征。PLGA纳米颗粒的包封率为88%。这些复合纳米颗粒很容易被A549细胞系摄取,且无细胞毒性或细胞毒性极小。本研究强调,复合纳米颗粒适用于将BSA递送至细胞,且无细胞毒性或细胞毒性很小,同时保持被包封BSA的完整性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a626/10233659/3fd053bb5aae/ao3c00738_0002.jpg

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