阿柏西普
血管抑制剂
化学
血管内皮生长因子
视网膜
变性(裂变材料)
黄斑变性
色谱法
生物物理学
圆二色性
药理学
眼科
生物化学
医学
血管内皮生长因子受体
外科
生物
内科学
贝伐单抗
核化学
化疗
作者
Miguel Moreno,Tan Su Teng Tabitha,Jayabalan Nirmal,Krishna Radhakrishnan,Colwin Yee,Serene B. Y. Lim,Subbu S. Venkatraman,Rupesh Agrawal
标识
DOI:10.1016/j.ejpb.2016.09.003
摘要
The anti-vascular endothelial growth factor (VEGF) agents such as ranibizumab (Lucentis®) and aflibercept (EyLea®) are currently used as monthly or bimonthly intravitreal injections to treat potentially retinal diseases such as wet age-related macular degeneration (AMD) or diabetic macular edema (DME). Because of the complications associated with repeated intra-vitreal injections, there is considerable interest in developing a sustained delivery system. The purpose of this study was to examine the stability of both therapeutic proteins under physiological conditions as well as when incorporated into drug delivery systems (DDS). First, thermotropic properties in physiological conditions and at different pH values were evaluated by differential scanning calorimetry (DSC) to determine the protein denaturation temperature. Second, the effects of pH and incubation time on conformational changes and aggregation were evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, and size-exclusion chromatography (SEC). Also, the ability of both proteins to bind to VEGF was tested in the aforementioned experimental conditions for up to 30 days. Finally, we investigated the stability of both proteins after a rapid screening method that simulates the first homogenizing step during the protein microencapsulation process. This method allowed the development of stable ranibizumab and aflibercept formulations that may be useful to entrap these proteins into microparticles selecting the most convenient organic solvent and protein stabilizers.
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