Hammer Maximilian, Herth Jonathan, Herbster Lorenz, Böhmann Manuel Ben, Muuss Marcel, Khoramnia Ramin, Scheuerle Alexander, Mier Walter, Wohlfart Sabrina, Auffarth Gerd Uwe, Uhl Philipp
University Eye Clinic Heidelberg, 69120 Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, 69047 Heidelberg, Germany.
Gels. 2024 Jul 28;10(8):501. doi: 10.3390/gels10080501.
Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application.
抗血管内皮生长因子(VEGF)药物,如贝伐单抗,用于视网膜手术,但其与硅油和新型水凝胶的相互作用仍不清楚。本研究考察了贝伐单抗在填充硅油的眼中与各种水凝胶替代物及猪玻璃体相比的体外药代动力学,以及其对硅油界面张力的影响。用平衡盐溶液平衡一个填充轻质或重质硅油、猪玻璃体或水凝胶(藻酸盐和聚乙二醇(PEG)基)的体外模型。对水相中贝伐单抗进行长达24小时的监测,并研究其对界面张力的影响。24小时后,观察到不同内填充材料中贝伐单抗的分配存在显著差异。在硅油中,贝伐单抗仅存在于水相中,而在其他内填充材料中,它在凝胶相中积累(在猪玻璃体中为96.1%,在藻酸盐中为83.5%,在PEG基水凝胶中为27.6%)。贝伐单抗显著降低了界面张力(从40到8 mN/m),可能增强了硅油乳化。内填充材料的类型对水相中贝伐单抗的浓度有很大影响。玻璃体和替代水凝胶可能充当药物储存库,这突出表明在临床应用前需要进行体内研究以探索这些相互作用。