In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System
In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System
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DOI：
10.1080/02713683.2017.1302590
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发表时间：
2017-01-01
影响因子：
2
通讯作者：
Kang-Mieler, Jennifer J.
中科院分区：
文献类型：
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作者：
Osswald, Christian R.;Guthrie, Micah J.;Kang-Mieler, Jennifer J.
目的：在体内证明微球-水凝胶药物递送系统 (DDS) 控制和延长释放低剂量的抗血管内皮生长因子 (抗 VEGF) 对激光诱导的脉络膜新生血管 (CNV) 大鼠模型具有治疗作用。方法：将抗 VEGF（雷珠单抗或阿柏西普）装入聚乳酸乙醇酸微球中，然后将其悬浮在注射剂中基于聚（N-异丙基丙烯酰胺）的热响应水凝胶DDS。之前的研究表明，DDS 可以释放具有生物活性的抗 VEGF，持续时间大约为 200 天。使用Ar-绿激光诱导CNV。四个实验组如下：（i）未治疗，（ii）无药物DDS，（iii）负载抗VEGF的DDS，和（iv）推注抗VEGF。 CNV 病变面积根据荧光素血管造影进行测量，并使用多 Otsu 阈值技术进行量化。在治疗前和治疗后（1、2、4、8和12周）还获得了眼压（IOP）和暗适应视网膜电图（ERG）。结果：在整个研究过程中，负载抗VEGF的DDS组的CNV病变面积明显小于未治疗的动物（60％）。注射后立即观察到眼压短暂短暂升高；然而，所有时间点的所有 IOP 测量值均在正常范围内。与载药 DDS 的治疗前测量结果相比，ERG 最大反应没有显着变化，这表明对视网膜细胞功能没有不利影响。结论：当前研究表明，DDS 可以有效减少小鼠模型中激光诱导的 CNV 损伤。我们的 DDS 的控释和缓释技术使用比推注给药少一个数量级的药物实现了更高的治疗效果。这表明我们的DDS可能在眼后段疾病的治疗中提供显着的优势。
Purpose: Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV).Methods: Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS. The DDS was shown previously to release bioactive anti-VEGF for similar to 200 days. CNV was induced using an Ar-green laser. The four experimental groups were as follows: (i) non-treated, (ii) drug-free DDS, (iii) anti-VEGF-loaded DDS, and (iv) bolus injection of anti-VEGF. CNV lesion areas were measured based on fluorescein angiograms and quantified using a multi-Otsu thresholding technique. Intraocular pressure (IOP) and dark-adapted electroretinogram (ERG) were also obtained pre- and post-treatment (1, 2, 4, 8, and 12 weeks).Results: The anti-VEGF-loaded DDS group had significantly smaller (60%) CNV lesion areas than non-treated animals throughout the study. A small transient increase in IOP was seen immediately after injection; however, all IOP measurements at all time points were within the normal range. There were no significant changes in ERG maximal response compared to pre-treatment measurements for the drug-loaded DDS, which suggests no adverse effects on retinal cellular function.Conclusions: The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.