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载吉西他滨的聚(丙交酯-乙交酯)-聚乙二醇金纳米粒子:评估制备方法对其物理化学特性、体外药物释放及细胞毒性的影响

Gemcitabine-loaded poly (lactide-co-glycolide) - poly (ethylene glycol) gold nanoparticles: Evaluating the effect of fabricating methods on physicochemical characteristics, in vitro drug release and cytotoxicity.

作者信息

Shakri Adibah, Mohd Paad Khairunnisa, Saad Norazalina, Mohamed Suffian Izzat Fahimuddin

机构信息

Department of Chemical and Environmental Engineering, Malaysia-Japan International Institute of Technology (MJIIT), Universiti Teknologi Malaysia Kuala Lumpur, 54100, Jalan Sultan Yahya Petra, Kuala Lumpur, Malaysia.

Department of Applied Science, Muroran Institute of Technology, Hokkaido, 050-8585, Japan.

出版信息

Drug Deliv Transl Res. 2025 Jun 4. doi: 10.1007/s13346-025-01884-y.

DOI:10.1007/s13346-025-01884-y
PMID:40465206
Abstract

Hybrid gold nanoparticles (AuNPs) are defined as a combination of organic and inorganic materials used as nanocarriers in the drug delivery system to enhance the performance of the drugs. Methods to fabricate the hybrid AuNPs such as double emulsion and nanoprecipitation require several steps and are inconsistent in their physicochemical characteristics limiting their application in drug delivery. The electrospray method has become a powerful tool for fabricating nanoparticles due to its simplicity, rapidity and consistency. Hence, this study aims to evaluate the performance of hybrid AuNPs prepared by two different methods; double emulsion and electrospray including the physicochemical characteristics, drug release profile and in vitro cytotoxicity. Hybrid AuNPs were prepared using double emulsion and electrospray methods. Then, the formed particles' hydrodynamic size, polydispersity index (PDI) and zeta potential were characterised using a Zetasizer Nano ZS. Furthermore, the drug release kinetics and cytotoxicity effects were evaluated using the dialysis method and the MTT assay. Hybrid AuNPs formed by the electrospray method (HAES) exhibit smaller particle sizes at 147.00 ± 10.4 nm with a PDI value of 0.35 ± 0.01 and zeta potential of -31.5 ± 2.6 compared to hybrid AuNPs formed using double emulsion methods (HADE) which exhibit larger particle sizes of 287.47 ± 1.87 nm with PDI value of 0.25 ± 0.09 and zeta potential of -23.30 ± 0.6. This study suggests that HAES prevent burst effects during drug release due to polymer composition changes under different temperatures that can enhance the drug delivery system. From the MTT assay, at 50 mg mL, the HAES exert higher toxicity effects of 50% compared to HADE due to different physicochemical characteristics and drug release patterns. These findings emphasise the advantage of the electrospray method in fabricating polymeric gold hybrid nanoparticles by forming smaller particle sizes, stable formulation, and higher toxicity to cancer cells compared to particle synthesis by the double emulsion method.

摘要

杂化金纳米颗粒(AuNPs)被定义为有机和无机材料的组合,用作药物递送系统中的纳米载体以提高药物性能。制备杂化AuNPs的方法,如双乳液法和纳米沉淀法,需要多个步骤,并且其物理化学特性不一致,限制了它们在药物递送中的应用。电喷雾法由于其简单、快速和一致性,已成为制备纳米颗粒的有力工具。因此,本研究旨在评估通过两种不同方法制备的杂化AuNPs的性能;双乳液法和电喷雾法,包括物理化学特性、药物释放曲线和体外细胞毒性。使用双乳液法和电喷雾法制备杂化AuNPs。然后,使用Zetasizer Nano ZS对形成颗粒的流体动力学尺寸、多分散指数(PDI)和zeta电位进行表征。此外,使用透析法和MTT法评估药物释放动力学和细胞毒性作用。与使用双乳液法(HADE)形成的杂化AuNPs相比,电喷雾法形成的杂化AuNPs(HAES)表现出更小的粒径,为147.00±10.4nm,PDI值为0.35±0.01,zeta电位为-31.5±2.6,而HADE的粒径更大,为287.47±1.87nm,PDI值为0.25±0.09,zeta电位为-23.30±0.6。本研究表明,HAES可防止药物释放过程中的突发效应,这是由于不同温度下聚合物组成的变化可增强药物递送系统。从MTT试验来看,在50mg/mL时,由于物理化学特性和药物释放模式不同,HAES比HADE具有更高的50%的毒性作用。这些发现强调了电喷雾法在制备聚合物金杂化纳米颗粒方面的优势,与双乳液法合成颗粒相比,它能形成更小的粒径、稳定的制剂,并且对癌细胞具有更高的毒性。

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