Name: slow-release drug delivery through elvax 40w to the rat retina: implications for the treatment of chronic conditions
Uploaded: 2014-09-17T13:00:00
Description: Watch this Scientific Journal Video about Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions at JoVE.com

This research was supported by the Australian Research Council through the ARC Centre of Excellence in Vision Science (CE0561903), the National Health and Medical Research Council (1049990), and Progetto regionale speciale multiasse 'Reti per l'Alta Formazione' - PO FSE Abruzzo 2007-2013 - Azione 4.II.iii.

进行的所有实验均按照ARVO声明眼科及视觉研究用动物，并与阿奎拉动物伦理委员会的大学和澳大利亚国立大学动物实验伦理委员会的批准。成年大鼠（P100-200）用于在本研究中。 1，准备共聚树脂颗粒<ol><li>将20的Elvax 40W的小球进入在通风橱内的小玻璃烧杯中。 </li><li>填用100％乙醇确保覆盖所有粒料的烧杯中。 </li><li>用封口膜封住烧杯中，并将其浸泡在100％乙醇中的粒料在?...

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本文证明了使用的药物 - 树脂复合物的药物缓释递送至视网膜。我们的目的是提出一种方法，它是相对便宜和容易在小动物模型适用。 鉴于APB的功能是作为一种谷氨酸类似物，它会阻止在眼睛的视网膜响应。结果表明，APB引起一个星期着床后的视网膜响应的堵塞。这表明，APB成功释放到玻璃体和视网膜，并且其作用仅限于眼睛的药物 - 树脂复合物注入。药物的全面影响变得?...

慢性疾病如糖尿病和高血压的治疗中提出了许多挑战，因为这些疾病通常需要治疗延长的时期，常常为生活。这叫做缓慢释放的药物递送系统，其减少需要频繁给药的发展。这些缓慢释放方法的有效性已经通过胰岛素泵的发展已经证明，减少治疗糖尿病需要胰岛素注射的次数。眼睛的慢性疾病，尤其是影响其内层，需要通过药物侵入性操作频繁给药。一个这样的慢性疾病，影响人的眼睛是年龄相关性黄斑变性（AMD）。它影响到中央视网膜，这是一个层位于负责发起视力的眼睛后面的神经组织。 AMD是导致失明的西方世界第一的主要原因。与治疗真是个特别的挑战tinal疾病是该药物是需要达到的眼睛，这经常需要递送的侵入性方法本深层。药物通常是给药于使用玻璃体内注射玻璃体腔和视网膜。然而，每次注射有一种postinjection并发症，包括眼内炎，视网膜脱离，白内障和玻璃体出血2的风险。这种风险被乘以与药物的每一个回注。 减少需要多次注射会在AMD的治疗的一个主要好处。治疗AMD，在新的血管生长是一个标志性的湿形式，既定的治疗策略是针对使用VEGF抑制剂3的血管内皮生长因子（VEGF）。目前，这是通过重复的玻璃体内注射递送。同样，在黄斑水肿，糖尿病性视网膜病变的常见并发症的治疗，皮质类固醇激素是通过反复注射交付<s达&gt; 4。通过缓慢释放的方式提供这些药物确实可以减少postinjection并发症的风险。 使用有机硅类橡胶车辆提供小分子进入动物组织5首次被描述缓慢释放的药物递送系统的概念。自那时以来，其他的缓慢释放的方法已被开发来提供更大的分子，其中一些在眼睛进行了测试。粒子的载体，如可生物降解的微球，聚交酯-共-乙交酯共聚物（PLGA）纳米颗粒和磷脂小泡（脂质体）可以作为运载工具6,7有用。 PLGA纳米颗粒和脂质体进行了比较， 在体外环境中为它们随着时间的推移7穿过巩膜递送抗癌剂的能力。这两款车均有效缓慢释放的药物。然而，该研究只在体外环境下进行。 Bochot 等人 （2002）8测试脂质体的效能，提供分子在体内的视网膜。他们已经证明，脂质体成功递送小的寡核苷酸对兔视网膜。作者认为脂质体可能是有益的视网膜疾病8的治疗。然而，这些小泡的性质在玻璃体漂浮装置，它们很可能会变得模糊或损害视力9。 冈部等人（2003）10中使用由33％的乙烯-乙酸乙烯酯的非生物可降解的聚合物的光盘适用的β-塞米松兔。它们植入光盘插入巩膜袋和演示的有效释放药物进入玻璃体和视网膜的长达一个月10。然而，在这种特定的协议中​​，植入物是相对大的和刚性的，并且需要更复杂的外科手术，包括一个大的巩膜切口和缝合。 早先的研究中调查了Tissu酒店ë响应于各种聚合物的车辆通过注入成兔眼的角膜，并发现，在醇洗涤的乙烯 - 乙酸乙烯酯共聚物并没有引起炎症或刺激。这些配合物显示出持续的递送较大的化合物的成动物组织为延长的时期，某些超过高达100天依赖于药物11。一个这种类型的共聚物树脂已开发工业中的Elvax 40W的形式（40％（重量）的乙烯 - 乙酸乙烯酯共聚单体含量用“W”酰胺添加剂以改善沉淀处理）。此共聚物树脂是一种惰性物质，其是稳定的，在室温和体温。它并没有被证明可导致在生物组织中的过敏或毒性。此树脂，有效地传递大量的各种药物在不同的实验模型，探讨各种系统，如乳腺导管系统12中，初级听觉皮层13,14 &lt;功能/ SUP&gt;，青蛙视觉系统15。这种树脂也被用于在眼睛将药物递送到显影龟16,17，鸡胚18,19，和成人鼬视网膜20。在大鼠中枢神经系统中，树脂仅被用于在大脑21-23，但其在大鼠眼用尚未记录。 使用该共聚物树脂慢慢将药物递送至视网膜方法比其他方法的优点是，它是一种不引起炎症或刺激的眼睛稳定的化合物。不同于粒子的载体，该药物 - 树脂复合物就不会在植入后损害视力的，因为它通常保持在输送，而不是浮在玻璃体的部位。这将只需要一个简单的植入过程进入玻璃体腔内靠近眼睛的角膜缘，并在植入后不会需要缝合。最近，出现了几种新颖的递送系统的出现，如封装的电池技术（ECT）24,25，水凝胶26和缩微胶片27。然而，在目前的研究中制备和输送的药物 - 树脂复合物所用的方法是既容易跟踪和便宜的，由此用于在基础研究环境中使用的更有利的。使用这种复合物能够提供长期的药物治疗的挑战是确定该药物，这将最大限度地具有较少的玻璃体内注射的治疗益处的最佳浓度。 本文旨在演示使用的药物 - 树脂复合物的长期治疗的成年大鼠视网膜。交付该模式的效果是用谷氨酸类似物2 - 氨基-4 - 膦酰（APB）作为药物测试。 APB块的ON双极细胞通过模仿谷氨酸，内源性神经递质在视网膜28的光响应。当建业竞争与谷氨酸受体，它会阻止二极管灯吨的回应。 APB已用于生理研究，以控制视网膜功能和使用电生理学方法，如电图（ERG）测量它的效果。在以前的研究中，APB已被用于短期29和长期治疗显影视网膜;后者所涉及的日常给予通过眼内注射单剂量为30天30。用APB的相同量（0.092毫克，无菌盐水，以50μM的浓度）为所有注射如以前的工作28,29,31建议。我们选择了APB以测试药物 - 树脂复合物作为缓释载体将药物递送到眼睛。在本研究中所述的方法类似的涉及药物-树脂复合物16,32的制备以前描述的方法;然而，我们也详细的使用特别是在成年大鼠的眼睛。后的APB-装载树脂进入眼睛的手术植入，ERG进行建立APB是否废除第retinal光响应，并且因此是否APB已经成功地释放到玻璃体和视网膜。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Elvax 40W Pellets</td>
			<td>Du Pont, DE, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dimethyl sulfoxide (DMSO)</td>
			<td>Sigma-Aldrich Co. LLC., MO, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>2-amino-4-phosphonobutyric acid (APB)</td>
			<td>Sigma-Aldrich Co. LLC., MO, USA</td>
			<td>A1910</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>Sigma-Aldrich Co. LLC., MO, USA</td>
			<td>34856</td>
			<td></td>
		</tr>
		<tr>
			<td>Fast Green FCF</td>
			<td>Sigma-Aldrich Co. LLC., MO, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Drierite, calcium sulfate</td>
			<td>Sigma-Aldrich Co. LLC., MO, USA</td>
			<td>238910</td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine, Ilium Ketamil</td>
			<td>Troy Laboratories Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Xylazine, Ilium Xylazil-20</td>
			<td>Troy Laboratories Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Atropine Sulphate, Minims eye drops</td>
			<td>Bausch &#38; Lomb Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tetracaine Hydrochloride, Minims eye drops</td>
			<td>Bausch &#38; Lomb Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Chloramphenicol, Chlorsig ointment</td>
			<td>Aspen Pharma Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Pentobarbital, Lethabarb</td>
			<td>Virbac Australia Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Lignocaine Hydrochloride, Ilium Lignocaine-20</td>
			<td>Troy Laboratories Pty. Ltd., NSW, Australia</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Uni-Core Punch Tool</td>
			<td>World Precision Instruments Inc., FL, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Curved Forceps</td>
			<td>World Precision Instruments Inc., FL, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Operating Microscope, Zeiss OPMI 99</td>
			<td>Zeiss, West Germany</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>25G Insulin Needle</td>
			<td>Terumo Corp., Tokyo, Japan</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dumont Tweezers</td>
			<td>World Precision Instruments Inc., FL, USA</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

slow-release drug delivery through elvax 40w to the rat retina: implications for the treatment of chronic conditions

视网膜疾病是难以治疗的视网膜深藏在眼内。通常需要药物递送的侵入性的方法来治疗这些疾病。慢性视网膜疾病，如视网膜水肿或新血管形成通常需要多眼内注射，以有效治疗该病症。然而，与这些注射相关的风险增加具有重复输送药物。因此，替代交付方式需要建立以尽量减少回注的风险。几个其他研究已开发的方法来递送药物在延长的时间，通过能够释放的化学物质慢慢进入眼睛的材料。在本次调查中，我们概述了使用的Elvax 40W，共聚物树脂，以充当药物输送到成年大鼠视网膜的车辆。的树脂制成，并装入该药物。该药物 - 树脂复合物，然后注入到玻璃体腔，在那里它会慢慢地释放药物比TI我。使用2 - 氨基-4 - 膦酰（APB），谷氨酸类似物阻止视网膜的光响应这种方法进行了测试。由此表明了该APB慢慢从树脂释放，并且能够阻止在植入后7天的视网膜响应。这表明，使用缓释药物递送该共聚物树脂可有效治疗视网膜上，并且可以用于治疗与进一步的测试。

全视野视网膜电图（ERG）被用于检测APB的视网膜上的效果。有关如何在ERG进行详细说明，请参阅下面的研究33,34。简言之，麻醉动物后，金电极被放置在眼睛的角膜上，和参考电极放置在两眼之间的前头皮，以记录视网膜的电活动。使用电子闪光灯单元中产生的刺激和10的强度不等，以10 6个光异构化反应，其表示每根棒的活化光敏分子的数目。在这些实验中，ERG记录采取了在1和后...

Watch this Scientific Journal Video about Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions at JoVE.com

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

本文详细介绍了如何的Elvax 40W，可作为药物输送到成年大鼠视网膜缓释方法。该协议的制备，装载和输送的药物 - 树脂复合物对眼睛进行说明。

通过40W的Elvax缓释给药的大鼠视网膜：对慢性疾病的治疗

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these ...

Research

JoVE Journal

Medicine

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

主动脉原位移植大鼠模型，研究慢性血管病变的发展

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

科研

医学

The Measurement and Treatment of Suppression in Amblyopia

测量和制止在弱视治疗

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

A Model of Chronic Nutrient Infusion in the Rat

在大鼠模型慢性营养输液

Chronic exposure to excessive levels of nutrients is postulated to  affect the function of several organs and tissues and to contribute to the  ...

Osmotic Drug Delivery to Ischemic Hindlimbs and Perfusion of Vasculature with Microfil for Micro-Computed Tomography Imaging

药物输送到微型计算机断层扫描成像缺血后肢血管灌注与微滤渗透

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to ...

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

异位黏膜移植程序直接给药到小鼠的大脑

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

腔内药物输送到鼠标动静脉瘘内皮

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The ...

Intravascular Delivery of Biologics to the Rat Kidney

生物血管内送货到大鼠肾脏

The renal microvascular compartment plays an important role in the progression of kidney disease and hypertension, leading to the development of End Stage ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

在耐药性颞叶癫痫患者卵圆孔电极记录的网络分析

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

经优化的 LC/ms 方法对囊性纤维化患者 Ivacaftor 及其主要代谢物和 Lumacaftor 的高通量分析

Defects in the cystic fibrosis trans-membrane conductance regulator (CFTR) are the cause of cystic fibrosis (CF), a disease with life-threatening ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

一种基于猪脑内皮细胞的体外血脑屏障模型的改进方法

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...