Simultaneous Release of Aflibercept and Dexamethasone from an Ocular Drug Delivery System.
Simultaneous Release of Aflibercept and Dexamethasone from an Ocular Drug Delivery System.
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阿非利西普和地塞米松在眼部给药系统中的同时释放。
DOI：
10.1080/02713683.2022.2053166
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发表时间：
2022-07
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
玻璃体内注射抗血管内皮生长因子（抗VEGF）是目前治疗继发于年龄相关性黄斑变性（AMD）的脉络膜新生血管（CNV）患者的标准。有越来越多的患者对抗VEGF单药治疗无反应。然而，一些患者对皮质类固醇和抗VEGF的联合治疗确实有反应。这种治疗需要每月/每两个月注射一次抗VEGF和每半年注射一次皮质类固醇。同时释放多种药物的药物输送系统（DDS）可以通过减少注射次数使这些患者受益。本研究的目的是表征阿柏西普和地塞米松从可生物降解的微粒-和纳米颗粒-水凝胶DDS中的同时释放。地塞米松负载的纳米粒子和aflibercept负载的微粒，分别使用改进的单和双乳液技术。然后，将微粒和纳米颗粒包埋到温度响应性、可生物降解的聚（乙二醇）-co-（L-乳酸）二丙烯酸酯（PEG-PLLA-DA）-N-异丙基丙烯酰胺（NIPAAm）水凝胶DDS中。用不同剂量的微粒和纳米颗粒进行DDS的药物释放研究和表征。载阿柏西普的微粒和载地塞米松的纳米颗粒-水凝胶的组合（Combo-DDS）实现了224天的总释放时间。与单药治疗阿柏西普负载微粒-水凝胶DDS（AFL-DDS）和单药治疗地塞米松负载纳米颗粒-水凝胶DDS（DEX-DDS）相比，Combo-DDS的膨胀比和平衡含水量略有下降。与AFL-DDS相比，Combo-DDS中阿柏西普的生物活性得以保持。Combo-DDS能够延长和控制阿柏西普和地塞米松从单个DDS中同时释放。这可以消除对湿性AMD患者单独的抗VEGF和皮质类固醇给药方案的需要。
Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to a combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.
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影响因子：
1.9
作者：
Kovach JL;Schwartz SG;Flynn HW Jr;Scott IU
通讯作者：
Scott IU
影响因子：
3.9
作者：
Falavarjani, K. Ghasemi;Nguyen, Q. D.
通讯作者：
Nguyen, Q. D.
影响因子：
1.9
作者：
Park YG;Rhu HW;Kang S;Roh YJ
通讯作者：
Roh YJ
影响因子：
17.8
作者：
El Sanharawi, M.;Kowalczuk, L.;Behar-Cohen, F.
通讯作者：
Behar-Cohen, F.
DOI：
10.1016/j.jcjo.2016.04.020
发表时间：
2016-08-01
影响因子：
4.2
作者：
Chaudhary, Varun;Barbosa, Joshua;Mohaghegh, S. Mohammad P.
通讯作者：
Mohaghegh, S. Mohammad P.