Novel electrospun implants of Sunitinib can depress ex-vivo ocular neovascularization

Deepakkumar Mishra, Hákon Hrafn Sigurðsson, A. P. Serro, G. Kalesnykas, R. Donnelly, R. Thakur
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引用次数: 1

Abstract

Choroidal neovascularization (CNV) is one of the hallmark symptoms of Wet Age-related Macular Degeneration (wAMD) and DiabeticRetinopathy(DR) which involves formation of neoangiogenic i.e. formation of new abnormal blood vessels emerging from the choroidal blood vessels and protruding through the retinal layer. The current management of wAMD involves intravitreal injections of anti-VEGF such as ranibizumab and aflibercept. We hypothesized the delivery of small molecule anti-angiogenesis agents such as the Sunitinib by episcleral route could be an effective and less challenging solution for the management of choroidal neovascularization. In this research, we have fabricated the sunitinib-loaded implants that are able of sustained the release of drug and possess improved ocular pharmacokinetics with a non-invasive administration. The novel episcleral implants were fabricated by electrospinning and were tested for different physiochemical and well as in-vitro pharmacokinetic properties. Further, these implants were tested for in-vitro biocompatibility and ex-vivo efficacy for the estimation of pharmacodynamic properties.
新型舒尼替尼电纺丝植入物可抑制离体眼新生血管
脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(wAMD)和糖尿病视网膜病变(DR)的标志性症状之一,它涉及新血管生成的形成,即从脉络膜血管中形成新的异常血管并突出视网膜层。目前wAMD的治疗包括玻璃体内注射抗vegf如雷尼单抗和阿非利西普。我们假设,小分子抗血管生成药物,如舒尼替尼,通过膜外途径递送可能是脉络膜新生血管管理的有效和较少挑战的解决方案。在这项研究中,我们制造了舒尼替尼负载的植入物,能够持续释放药物,并且具有改善的眼药代动力学和非侵入性给药。采用静电纺丝法制备了新型外膜植入物,并对其进行了不同的理化和体外药代动力学性能测试。此外,这些植入物进行了体外生物相容性和离体功效测试,以估计药效学特性。
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