Treatment Efficacy and Biocompatibility of a Biodegradable Aflibercept-Loaded Microsphere-Hydrogel Drug Delivery System.

Treatment Efficacy and Biocompatibility of a Biodegradable Aflibercept-Loaded Microsphere-Hydrogel Drug Delivery System.
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DOI:
10.1167/tvst.9.11.13
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发表时间:
2020-10
影响因子:
3
通讯作者:
Kang-Mieler JJ
Kang-Mieler JJ
中科院分区:
医学3区
文献类型:
--
作者:
Liu W;Tawakol AP;Rudeen KM;Mieler WF;Kang-Mieler JJ

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评价生物可降解阿柏西普微球-水凝胶给药系统(DDS)在激光诱导的脉络膜新生血管(CNV)大鼠模型中的体内治疗效果和生物相容性。CNV诱导两周后,将动物随机分配到四个实验组:(1)未治疗,(2)单次玻璃体内(IVT)注射空白DDS,(3)每两个月一次IVT推注阿柏西普注射,和(4)单次IVT注射阿柏西普-DDS。使用荧光血管造影术和多大津阈值法纵向监测CNV病变大小6个月。对于安全性和生物相容性评估,另外三只非CNV动物接受空白DDS注射。进行视网膜电图、眼压和临床检眼镜检查。第0周(治疗干预)的平均病变面积为(1)未治疗组8693 ± 628 µm2,(2)空白DDS组8261 ± 709 µm2,(3)推注组10,368 ± 885 µm2,(4)aflibercept-DDS组10,306 ± 1212 µm2。对于未治疗组,CNV病变大小在第2周增加,并在整个研究期间保持增加。治疗组在第2周后表现出CNV尺寸减小,并保持6个月。22周时,上述相应组CNV病变面积的平均百分比变化分别为+38.87% ± 7.08%、+34.19% ± 9.93%、-25.95% ± 3.51%和-32.69% ± 5.40%。没有发现慢性炎症和其他眼部异常的迹象。aflibercept-DDS治疗CNV病变有效6个月,是安全的,耐受性好,生物相容性好。拟议的DDS是一个有前途的系统,以减少抗血管内皮生长因子治疗的IVT注射频率。
To evaluate the in vivo treatment efficacy and biocompatibility of a biodegradable aflibercept-loaded microsphere-hydrogel drug delivery system (DDS) in a laser-induced choroidal neovascularization (CNV) rat model. Two weeks after CNV induction, animals were randomly assigned into four experimental groups: (1) no treatment, (2) single intravitreal (IVT) injection of blank DDS, (3) bimonthly bolus IVT aflibercept injections, and (4) single IVT injection of aflibercept-DDS. CNV lesion sizes were monitored longitudinally using fluorescence angiography and multi-Otsu thresholding for 6 months. For safety and biocompatibility assessment, an additional three non-CNV animals received a blank DDS injection. Electroretinogram, intraocular pressure, and clinical ophthalmoscopic examinations were performed. The average lesion areas at week 0 (treatment intervention) were (1) 8693 ± 628 µm2 for no treatment, (2) 8261 ± 709 µm2 for blank DDS, (3) 10,368 ± 885 µm2 for bolus, and (4) 10,306 ± 1212 µm2 for aflibercept-DDS. For the nontreated groups, CNV lesion size increased by week 2 and remained increased throughout the study. The treated groups exhibited CNV size reduction after week 2 and remained for 6 months. At week 22, the average percent changes in CNV lesion area were +38.87% ± 7.08%, +34.19% ± 9.93%, –25.95% ± 3.51%, and –32.69% ± 5.40% for the above corresponding groups. No signs of chronic inflammation and other ocular abnormalities were found. The aflibercept-DDS was effective in treating CNV lesions for 6 months and is safe, well tolerated, and biocompatible. The proposed DDS is a promising system to reduce IVT injection frequency for anti–vascular endothelial growth factor treatment.
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