Radhakrishnan Krishna, Vincent Anita, Joseph Rini Rachel, Moreno Miguel, Dickescheid Andreas, Agrawal Rupesh, Venkatraman Subbu
NTU-Northwestern Institute for Nanomedicine (NNIN), School of Materials Science and Engineering, Nanyang Technological University (NTU), 50, Nanyang Avenue, Singapore 639798, Singapore.
Tan Tock Seng Hospital, Novena, Singapore 308433, Singapore.
Pharmaceutics. 2019 Jul 11;11(7):330. doi: 10.3390/pharmaceutics11070330.
Diseases affecting the posterior segment of the eye such as age-related macular degeneration and diabetic retinopathy are leading causes of blindness all over the world. The current treatment regimen for such diseases involves repeated intravitreal injections of anti- Vascular Endothelial Growth Factor (VEGF) proteins. This method is highly invasive and can lead to severe complications. In an attempt to develop less invasive alternatives, we propose the use of a controlled release system consisting of anti-VEGF loaded hollow microcapsules that can be administered periocularly to form drug eluting depots on the episcleral surface. The microcapsules with either positive or negative surface charge were prepared by a layer by layer approach and showed pH responsive permeability switching. An ex vivo experiment using porcine sclera indicated positively charged microcapsules remained on the episcleral surface over four days while the negatively charged microcapsules were washed away. These positively charged microcapsules were then loaded with anti-VEGF protein ranibizumab using pH dependent permeability switching and protein release from the microcapsules were studied using an in vitro setup. An ex vivo experiment utilizing porcine sclera demonstrated sustained release of ranibizumab over seven days with zero-order kinetics.
影响眼后段的疾病，如年龄相关性黄斑变性和糖尿病视网膜病变，是全球失明的主要原因。目前针对此类疾病的治疗方案包括反复玻璃体内注射抗血管内皮生长因子（VEGF）蛋白。这种方法具有高度侵入性，并且可能导致严重并发症。为了开发侵入性较小的替代方案，我们提议使用一种控释系统，该系统由负载抗VEGF的中空微胶囊组成，可通过眼周给药在巩膜表面形成药物洗脱库。通过层层组装法制备了具有正表面电荷或负表面电荷的微胶囊，并显示出pH响应性渗透转换。使用猪巩膜进行的体外实验表明，带正电荷的微胶囊在巩膜表面停留了四天，而带负电荷的微胶囊被冲走了。然后利用pH依赖性渗透转换将抗VEGF蛋白雷珠单抗负载到这些带正电荷的微胶囊中，并使用体外装置研究微胶囊中蛋白质的释放。利用猪巩膜进行的体外实验表明，雷珠单抗以零级动力学持续释放超过七天。
