pH-responsive chitosan copolymer synthesized via click chemistry for design of polymeric nanoparticles for targeted drug delivery

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Carbohydrate Research Pub Date : 2024-07-02 DOI:10.1016/j.carres.2024.109200

Mariya Gover Antoniraj, Henry Linda Jeeva Kumari, A. Shanmugarathinam, Ruckmani Kandasamy

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Abstract

The polymeric nanoparticles (PNPs) loaded with prednisolone were developed to exhibit pH-responsive properties owing to the attachment of a hydrazone linkage between the copolymer chitosan and mPEG. In the diseased cellular environment, the hydrazone bond tends to break due to reduced pH, leading to the release of the drug from the PNPs at the required site of action. The fabricated PNPs exhibit spherical morphology, optimum size (∼200 nm), negative surface charge, and monodispersed particle size distribution. The encapsulation efficiency of the PNPs was determined to be 71.1 ± 0.79 % and two experiments (polymer weight loss and drug release) confirmed the pH-responsive properties of the PNPs. The cellular study cytotoxicity assay showed biocompatibility of PNPs and drug molecule-mediated toxicity to A549 cells. The ligand atrial natriuretic peptide-attached PNPs internalized into A549 cells via natriuretic peptide receptor-A to achieve target specificity. The PNPs cytotoxicity and pH-response medicated inflammation reduction functionality was studied in inflammation-induced RAW264.7 cell lines. The study observed the PNPs effectively reduced the inflammatory mediators NO and ROS levels in RAW264.7. The results showed that pH-responsive properties of PNPs and this novel fabricated delivery system effectively treat inflammatory and cancer diseases.

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通过点击化学合成的 pH 响应壳聚糖共聚物，用于设计靶向给药的聚合物纳米颗粒。

由于共聚物壳聚糖和 mPEG 之间的腙连接具有 pH 响应特性，因此开发出了负载泼尼松龙的聚合物纳米粒子（PNPs）。在病变的细胞环境中，由于 pH 值降低，腙键容易断裂，导致药物从 PNPs 释放到所需的作用部位。制备的 PNPs 呈球形，具有最佳尺寸（200 nm）、负表面电荷和单分散粒度分布。经测定，PNPs 的封装效率为 71.1 ± 0.79 %，两项实验（聚合物失重和药物释放）证实了 PNPs 的 pH 响应特性。细胞研究细胞毒性测定显示了 PNPs 的生物相容性和药物分子介导的对 A549 细胞的毒性。配体心房钠尿肽附着的 PNPs 通过钠尿肽受体-A 内化到 A549 细胞中，实现了靶向特异性。在炎症诱导的 RAW264.7 细胞系中研究了 PNPs 的细胞毒性和 pH 响应药物消炎功能。研究发现，PNPs 能有效降低 RAW264.7 细胞中的炎症介质 NO 和 ROS 水平。研究结果表明，PNPs 的 pH 响应特性和这种新型制造的递送系统能有效治疗炎症和癌症疾病。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".

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