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B-179 Comparative Evaluation of Cisplatin Release from Alginate Hydrogels with Embedded Silver Nanoparticles: An HPLC and Colorimetric Spectrophotometry Study
Clinical Chemistry ( IF 7.1 ) Pub Date : 2024-10-02 , DOI: 10.1093/clinchem/hvae106.539
H Kalil, S Maher, M Bayachou

Background Cisplatin [cis-dichlorodiamine platinum (II)], is a well-recognized chemotherapeutical drug. Cisplatin has been employed in treating a wide range of human cancers, such as those of the breast, bladder, lung, ovarian, and testicular cancers. Its therapeutic action is attributed to its capacity to form crosslinks with the DNA's purine bases, disrupting DNA repair processes, causing DNA damage, and ultimately leading to apoptosis in cancerous cells. Nonetheless, the application of cisplatin is constrained by the development of multidrug resistance and the occurrence of severe adverse effects, including nephrotoxicity, bone marrow suppression, hearing loss, allergic responses, nerve damage, and low magnesium levels in the blood. Numerous strategies have been explored to enhance the anticancer effectiveness of cisplatin while minimizing its associated toxicities. These strategies include combination therapies that incorporate nanoparticles, liposomes, and polymer micelles. In this project, cisplatin was embedded into alginate hydrogels loaded with silver nanoparticles and in vitro cisplatin release study using HPLC and UV-Vis spectrophotometry were studied. Methods We developed a novel nanocomplex by integrating silver nanoparticles (AgNPs) with alginate hydrogel coating to create a versatile platform for drug delivery. To incorporate the chemotherapeutic agent, cisplatin (150 ppm) was introduced into the AgNPs-alginate mixture utilizing rapid stirring to ensure uniform distribution and encapsulation of cisplatin within the nanocomplex. A range of analytical methods, such as UV-Vis, FTIR, SEM/EDX, and Zeta potential analysis, were employed to characterize the nanocomplex. To evaluate cisplatin release kinetics from the nanocomplex, we employed an in vitro dialysis method for monitoring its sustained release. High-performance liquid chromatography (HPLC) was used for precise cisplatin release quantification, then validated by colorimetric spectrophotometry. This dual-method approach ensured accurate insights into the nanocomplex’s release dynamics, substantiating its potential in enhancing targeted cancer therapy through advanced drug delivery systems. Results The analysis through UV-Vis revealed an absorption spectrum around 410 nm, indicative of the characteristic plasmon resonance associated with silver nanoparticles. TEM provided high-resolution imagery, revealing that the size of the silver nanoparticles varied between 4 and 30 nm, averaging at 13 nm with a standard deviation of 5 nm specifically for the alginate-coated AgNPs. SEM images confirmed the anticipated spherical distribution of silver nanoparticles within the alginate hydrogel framework. EDX spectroscopy analysis further verified the incorporation of silver nanoparticles and platinum within the complex. The cisplatin release studies from this newly developed nanocomplex illustrated a prolonged, slow, and consistent release pattern, extending over days, in stark contrast to the rapid and complete release of cisplatin from its unbound state, which achieved peak release within an hour. Conclusions In this study, we successfully developed and validated an innovative, multifunctional nanoplatform for drug delivery, comprising alginate hydrogel synergistically co-loaded with silver nanoparticles (AgNPs) and cisplatin. This novel drug carrier system demonstrated a marked enhancement in the controlled delivery of cisplatin, evidenced by the slow and sustained release profile observed over three days. The slow and sustained release of cisplatin from the alginate complex, compared to the free form, highlights the efficacy of the nanoplatform in modulating the drug’s release kinetics.

中文翻译:


B-179 嵌有银纳米颗粒的藻酸盐水凝胶中顺铂释放的比较评估:HPLC 和比色分光光度法研究



背景顺铂[顺式二氯二胺铂(II)]是一种公认​​的化疗药物。顺铂已用于治疗多种人类癌症,例如乳腺癌、膀胱癌、肺癌、卵巢癌和睾丸癌。其治疗作用归因于其与 DNA 嘌呤碱基形成交联的能力,破坏 DNA 修复过程,造成 DNA 损伤,并最终导致癌细胞凋亡。尽管如此,顺铂的应用受到多药耐药性的发展和严重不良反应的发生的限制,包括肾毒性、骨髓抑制、听力损失、过敏反应、神经损伤和血液中镁含量低。人们已经探索了许多策略来增强顺铂的抗癌效果,同时最大限度地减少其相关毒性。这些策略包括结合纳米颗粒、脂质体和聚合物胶束的联合疗法。在该项目中,将顺铂嵌入负载有银纳米颗粒的藻酸盐水凝胶中,并利用高效液相色谱法和紫外-可见分光光度法进行体外顺铂释放研究。方法我们通过将银纳米颗粒 (AgNP) 与藻酸盐水凝胶涂层相结合,开发了一种新型纳米复合物,以创建一个多功能的药物输送平台。为了掺入化疗剂,利用快速搅拌将顺铂 (150 ppm) 引入 AgNPs-藻酸盐混合物中,以确保顺铂在纳米复合物内的均匀分布和封装。采用 UV-Vis、FTIR、SEM/EDX 和 Zeta 电位分析等一系列分析方法来表征纳米复合物。 为了评估纳米复合物的顺铂释放动力学,我们采用体外透析方法来监测其持续释放。使用高效液相色谱 (HPLC) 对顺铂释放进行精确定量,然后通过比色分光光度法进行验证。这种双重方法确保了对纳米复合物释放动力学的准确了解,证实了其通过先进的药物输送系统增强靶向癌症治疗的潜力。结果 UV-Vis 分析揭示了 410 nm 左右的吸收光谱,表明与银纳米颗粒相关的特征等离子共振。 TEM 提供了高分辨率图像,显示银纳米颗粒的尺寸在 4 至 30 nm 之间变化,平均为 13 nm,标准偏差为 5 nm,特别是对于藻酸盐涂层的 AgNP。 SEM 图像证实了银纳米颗粒在藻酸盐水凝胶框架内的预期球形分布。 EDX 光谱分析进一步验证了复合物中银纳米粒子和铂的结合。这种新开发的纳米复合物的顺铂释放研究表明,它具有延长数天的延长、缓慢和一致的释放模式,这与顺铂从其未结合状态快速且完全释放形成鲜明对比,顺铂在一个小时内达到峰值释放。结论 在这项研究中,我们成功开发并验证了一种用于药物输送的创新型多功能纳米平台,其中包含与银纳米颗粒 (AgNP) 和顺铂协同负载的藻酸盐水凝胶。 这种新型药物载体系统在顺铂的受控递送方面表现出显着增强,三天内观察到的缓慢且持续的释放曲线证明了这一点。与游离形式相比,顺铂从藻酸盐复合物中缓慢而持续地释放,凸显了纳米平台在调节药物释放动力学方面的功效。
更新日期:2024-10-02
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