Long-term release of fluocinolone acetonide using biodegradable fumarate-based polymers
Long-term release of fluocinolone acetonide using biodegradable fumarate-based polymers
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DOI：
10.1016/j.jconrel.2006.05.024
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发表时间：
2006-08-28
影响因子：
10.8
通讯作者：
Mikos, A. G.
中科院分区：
文献类型：
--
作者：
Haesslein, A.;Ueda, H.;Mikos, A. G.
由可生物降解聚合物制成的眼内给药系统在有效治疗眼后段慢性疾病方面具有巨大的潜力。本研究基于这样的假设：基于交联聚富马酸丙烯（PPF）的基质由于其疏水性和网络密度，是抗炎药氟西诺酮醋酸酯（FA）缓释的合适的长期递送装置。利用PPF与n -乙烯基吡咯烷酮（NVP）光交联制备了长10 mm、直径0.6 mm的fa负载棒。采用高效液相色谱法测定FA和NVP的释放量。采用2（3-1）因子设计研究了载药量和PPF与NVP的比例对释放动力学的影响。总的来说，所有测试配方的FA释放在体外持续了近400天。低爆发释放之后是由扩散和大块侵蚀控制的双模式释放，释放速率高达1.7 μ g/天。药物的负荷和基质组成控制了药物的爆发效应程度和释放动力学。用重量法测定了基质含水量和降解率。显微计算机断层扫描成像的结构和尺寸的变化。结果表明，基于光交联ppf的基质是一种很有前途的长期眼内给药装置。(c) 2006 Elsevier B.V.版权所有
Intraocular drug delivery systems made from biodegradable polymers hold great potential to effectively treat chronic diseases of the posterior segment of the eye. This study is based on the hypothesis that crosslinked poly(propylene fumarate) (PPF)-based matrices are suitable long-term delivery devices for the sustained release of the anti-inflammatory drug fluocinolone acetonide (FA) due to their hydrophobicity and network density. FA-loaded rods of 10 mm length and 0.6 mm diameter were fabricated by photo-crosslinking PPF with N-vinyl pyrrolidone (NVP). The released amounts of FA and NVP were determined by HPLC analysis. The effects of drug loading and the ratio of PPF to NVP on the release kinetics were investigated using a 2(3-1) factorial design. Overall, FA release was sustained in vitro over almost 400 days by all tested formulations. Low burst release was followed by a dual modality release controlled by diffusion and bulk erosion with release rates up to 1.7 mu g/day. The extent of the burst effect and the release kinetics were controlled by the drug loading and the matrix composition. Matrix water content and degradation were determined gravimetrically. Micro-computed tomography was used to image structural and dimensional changes of the devices. The results show that photo-crosslinked PPF-based matrices are promising long-term delivery devices for intraocular drug delivery. (c) 2006 Elsevier B.V. All rights reserved.