通过体外生物相容性和药物装置相互作用评估眼内给药镁基组分。

Marco Ferroni, Francesco De Gaetano, Manuela Zonfrillo, Nina Bono, Matteo Giuseppe Cereda, Pasquale Pierimarchi, Gianluca Sferrazza, Gabriele Candiani, Federica Boschetti
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引用次数: 0

摘要

镁基眼内给药装置的开发对生物医学应用具有重要的前景,特别是在使用血管内皮生长因子(VEGF)抑制剂(如贝伐单抗)治疗湿性年龄相关性黄斑变性(AMD)方面。镁的快速降解,可以很好地调节以实现AMD治疗所需的控制释放,以及其完善的生物相容性和可生物降解特性,使其成为这些应用的理想材料。该研究旨在通过证明单克隆抗体(特别是贝vacizumab)在镁腐蚀产物存在下的稳定性,以及这些产物与各种细胞系(包括小鼠成纤维细胞(3T3)、大鼠视网膜上皮细胞(RMC-1)和人视网膜色素上皮细胞(ARPE19))的生物相容性,评估镁作为眼部药物输送系统载体的潜力。贝伐单抗含纯镁(Mg)的稳定性通过间接ELISA方案进行了研究,该方案是为此特定目的开发和定制的。Mg腐蚀产物的生物相容性通过MTT和台盼蓝活性测定以及细胞周期分析进行毒理学评价。结果显示,Mg腐蚀产物对贝伐单抗的稳定性没有显著影响,其平均值的变化始终低于或等于10%。此外,Mg提取物显示出最小的细胞毒性,因为所有细胞系的代谢活性都超过80%,根据ISO 10993-5标准,Mg提取物被列为0/1级细胞毒性。在长达72小时的暴露中,细胞活力、增殖和形态未受影响。本研究首次在体外评估了贝伐珠单抗在镁腐蚀产物存在下的稳定性及其与视网膜细胞系的生物相容性,为未来的眼科研究奠定了基础,并强调了镁作为眼内给药系统材料的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessment of magnesium-based components for intraocular drug delivery byin vitrobiocompatibility and drug-device interaction.

The development of magnesium-based intraocular drug delivery devices holds significant promise for biomedical applications, particularly in treating wet age-related macular degeneration (AMD) using vascular endothelial growth factor inhibitors such as bevacizumab. Magnesium's rapid degradation, which can be finely tuned to achieve the controlled release required for AMD treatment, along with its well-established biocompatibility and biodegradable properties, positioning it as an ideal material for these applications. The study aimed to evaluate magnesium's potential as a carrier for ocular drug delivery systems by demontrating the stability of monoclonal antibodies, specifically bevacizumab, in the presence of magnesium corrosion products and the biocompatibility of these products with various cell lines, including murine fibroblasts (3T3), rat retinal Müller cells, and human retinal pigment epithelial cells (ARPE19). The stability of bevacizumab with pure magnesium (Mg) was investigated through an indirect enzyme-linked immunosorbent assay protocol, developed and customized for this specific aim. The biocompatibility of Mg corrosion products was assessed by toxicological evaluations through MTT and Trypan Blue Viability assays, along with cell cycle analysis. Results demonstrated no significant impact of Mg corrosion products on bevacizumab stability, with changes in mean values consistently below or equal to 10%. Furthermore, Mg extracts showed minimal cytotoxicity, as metabolic activity exceeded 80% across all cell lines, classified as Grade 0/1 cytotoxicity under ISO 10993-5 standards. Cell viability, proliferation, and morphology remained unaffected for up to 72 h of exposure. This study provides the firstin vitroevaluation of bevacizumab's stability in the presence of magnesium corrosion products and its biocompatibility with retinal cell lines, laying the foundation for future ophthalmic research and underscoring magnesium's potential as a material for intraocular drug delivery systems.

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