作者要感谢杰米翠的技术工作。这项工作是支持的，部分由研究资助SC CTSI NIH / NCRR / NCATS - UL1TR000130（DLD），AA022448（DLD）和药房的南加州大学。此外，含IVM快速溶解口服片经固化药业（奥克斯纳德，CA）的友情提供。

描述的所有程序已经批准了南加州大学的机构动物护理和使用委员会（IACUC）。 1.动物处理和习惯化<ol><li>介绍<ol><li>允许小鼠适应的饲养条件和处理实验技术，在随后的给药方法减少压力。在此期间，记录体重和各小鼠的食物摄入;如果需要的话，它们可以在以后用作非侵入点比较，以评估药物毒性（可选）的。前者也可用于确定基于重量的药物剂量。 注意:有趣的是，应根据实验者与动物相互作用的数目来确定的习惯期的长短。根据我们的经验，在C57BL / 6J品系小鼠已观察到有麻烦我们典型的为期一周的习惯时间内超过〜5人habituating搬运。如果可行的话，我们也鼓励实验者（S）使用香味乳液，香皂，香水和处理动物之前与以前的报告表明新的刺激，如气味，可能会阻碍习惯11期不要。 </li></ol></li><li>脚步<ol><li>研究开始前至少5天开始，将动物转移到在其中随后的实验将发生室。 </li><li>牢牢抓住尾巴的中间，轻轻提起动物出笼子，进入重船记录鼠标的重量。 <ol><li>一旦放置在标尺上的鼠标，因为它是在记提升出cagekeeping的适当掌握尾部的内侧/近侧方面中，以避免脱套伤，抓尾部12的远侧方面时可能发生。 </li><li>记录的权重值，一旦老鼠已被安全地放置在权衡船。 </li></ol></li><li>记录食物的重量为RECOM谁料连续2天，以建立基线的食品消费水平将会在实验过程中13帮助捕获潜在的毒性。 </li></ol></li></ol> 2.准备喂食针的，蔗糖溶液，与个人ODS <ol><li>使用高压釜灭菌的不锈钢管饲针头在用于实验的准备。准备2根/基和1个另外的针被用作后备如果需要的话。 注意:此研究利用1.5英寸，弯曲的，18 G，不锈钢在针的末端馈送带有2.25毫米球针。 </li><li> 20ml水加至0.85克蔗糖以创建一个4.25％（重量/体积）的蔗糖溶液。 注:根据正在评估其他低剂量蔗糖的参数可能也可使用14。 </li><li>通过切割标准的矩形试片成片是在直径为0.5厘米英寸制备每个动物的口腔溶解条（ODS）我们ING市售的单季英寸的孔，打孔机。在此演示中使用矩形试验片制成含有6毫克伊维菌素（IVM），并切成此大小时，分配一个0.21毫克剂量将每个独立的圆形片近似10毫克/公斤的剂量为每只动物（我们的期望的剂量/动物）。此剂量可通过浓缩/在矩形条稀释整体制剂和/或切断所述带状成不同尺寸来调整。 </li></ol> 3.药物 - 送货<ol><li>如先前在步骤1.1-1.2中所述记录重量值。 </li><li>记录重量后，将鼠标移动到金属网格笼子顶部。一旦出现，使用占主导地位的拇指，食指，和第三的手指，轻轻地拉回来的尾巴。这将导致鼠标无意中夹住金属丝笼顶部和伸出它的后面，伸展它的身体从实验者路程。 </li><li>把握颈背与非待办事项minant拇指，食指，和第三手指舒适地抑制所述动物用把手是安全。 注意:用较小的手的实验者也可以使用4 个手指，同一只手的，拉回背面的颈背，将获得的小鼠的更安全的保持状态。另外，根据个人喜好，无名指和/或小指也可以用于固定尾巴然而这是没有必要的12。 </li><li>按住鼠标在直立位置。 </li><li>注意:观察小鼠的粘膜的颜色。紫色/蓝色的外观是一个迹象表明实验者得太紧收紧颈背和鼠标无法呼吸。 <ol><li>如果发生这种情况，立即把鼠标放在铁笼顶部回落，并允许它重新尝试抑制动物之前休息2-3〜分钟。 </li></ol></li><li>浸没灌胃针的灯泡尖端4.25％蔗糖溶液以用作促味剂粘合剂的消耗臭氧层物质。 </li><li>向下按压与灌胃针的尖泡一个预切的消耗臭氧层物质的口腔溶解条连接。 </li><li>通过将其鼻孔和/或口附近目前的消耗臭氧层物质的老鼠，并让动物消耗薄膜。可替代地，ODS可以通过直接放置在薄带到舌头的小鼠吞局部递送到口腔。 </li><li>药物剂量会期间更换针头中期组，以防止感染扩散。 </li></ol>

<ol><li>Brown, A. P., Dinger, N., Levine, B. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Stress+produced+by+gavage+administration+in+the+rat%5BTitle%5D)+AND+%22Contemp+Top+Lab+Anim+Sci%22%5BJournal%5D)">Stress produced by gavage administration in the rat.</a> Contemp Top Lab Anim Sci. 39 (1), 17-21 (2000).</li>
<li>Gonzales, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Alternative+method+of+oral+administration+by+peanut+butter+pellet+formulation+results+in+target+engagement+of+BACE1+and+attenuation+of+gavage-induced+stress+responses+in+mice%5BTitle%5D)+AND+%22Pharmacol+Biochem+Behav%22%5BJournal%5D)">Alternative method of oral administration by peanut butter pellet formulation results in target engagement of BACE1 and attenuation of gavage-induced stress responses in mice.</a> Pharmacol Biochem Behav. 126, 28-35 (2014).</li>
<li>Walker, M. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+less+stressful+alternative+to+oral+gavage+for+pharmacological+and+toxicological+studies+in+mice%5BTitle%5D)+AND+%22Toxicol+Appl+Pharmacol%22%5BJournal%5D)">A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.</a> Toxicol Appl Pharmacol. 260 (1), 65-69 (2012).</li>
<li>Zhang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Voluntary+oral+administration+of+drugs+in+mice%5BTitle%5D)+AND+%22Protocol+Exchange%3A+Nature+Publishing+Group%22%5BJournal%5D)">Voluntary oral administration of drugs in mice.</a> Protocol Exchange: Nature Publishing Group. , (2011).</li>
<li>Froehlich, J. C., Hausauer, B. J., Federoff, D. L., Fischer, S. M., Rasmussen, D. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prazosin+reduces+alcohol+drinking+throughout+prolonged+treatment+and+blocks+the+initiation+of+drinking+in+rats+selectively+bred+for+high+alcohol+intake%5BTitle%5D)+AND+%22Alcohol+Clin+Exp+Res%22%5BJournal%5D)">Prazosin reduces alcohol drinking throughout prolonged treatment and blocks the initiation of drinking in rats selectively bred for high alcohol intake.</a> Alcohol Clin Exp Res. 37 (9), 1552-1560 (2013).</li>
<li>Goldkuhl, R., Carlsson, H. E., Hau, J., Abelson, K. S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+subcutaneous+injection+and+oral+voluntary+ingestion+of+buprenorphine+on+post-operative+serum+corticosterone+levels+in+male+rats%5BTitle%5D)+AND+%22Eur+Surg+Res%22%5BJournal%5D)">Effect of subcutaneous injection and oral voluntary ingestion of buprenorphine on post-operative serum corticosterone levels in male rats.</a> Eur Surg Res. 41 (3), 272-278 (2008).</li>
<li>Marx, J. O., Vudathala, D., Murphy, L., Rankin, S., Hankenson, F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Antibiotic+administration+in+the+drinking+water+of+mice%5BTitle%5D)+AND+%22J+Am+Assoc+Lab+Anim+Sci%22%5BJournal%5D)">Antibiotic administration in the drinking water of mice.</a> J Am Assoc Lab Anim Sci. 53 (3), 301-306 (2014).</li>
<li>Ferguson, S. A., Boctor, S. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Use+of+food+wafers+for+multiple+daily+oral+treatments+in+young+rats%5BTitle%5D)+AND+%22J+Am+Assoc+Lab+Anim+Sci%22%5BJournal%5D)">Use of food wafers for multiple daily oral treatments in young rats.</a> J Am Assoc Lab Anim Sci. 48 (3), 292-295 (2009).</li>
<li>Turner, P. V., Brabb, T., Pekow, C., Vasbinder, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Administration+of+substances+to+laboratory+animals%3A+routes+of+administration+and+factors+to+consider%5BTitle%5D)+AND+%22J+Am+Assoc+Lab+Anim+Sci%22%5BJournal%5D)">Administration of substances to laboratory animals: routes of administration and factors to consider.</a> J Am Assoc Lab Anim Sci. 50 (5), 600-613 (2011).</li>
<li>Bala, R., Pawar, P., Khanna, S., Arora, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Orally+dissolving+strips%3A+A+new+approach+to+oral+drug+delivery+system%5BTitle%5D)+AND+%22Int+J+Pharm+Investig%22%5BJournal%5D)">Orally dissolving strips: A new approach to oral drug delivery system.</a> Int J Pharm Investig. 3 (2), 67-76 (2013).</li>
<li>Potashkin, J. A., Blume, S. R., Runkle, N. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Limitations+of+animal+models+of+Parkinson%27s+disease%5BTitle%5D)+AND+%22Parkinsons+Dis%22%5BJournal%5D)">Limitations of animal models of Parkinson's disease.</a> Parkinsons Dis. 2011, (2010).</li>
<li>Machholz, E., Mulder, G., Ruiz, C., Corning, B. F., Pritchett-Corning, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Manual+restraint+and+common+compound+administration+routes+in+mice+and+rats%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments+JoVE%22%5BJournal%5D)">Manual restraint and common compound administration routes in mice and rats.</a> Journal of Visualized Experiments JoVE. (67), e2771(2012).</li>
<li>Yardley, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Ivermectin+reduces+alcohol+intake+and+preference+in+mice%5BTitle%5D)+AND+%22Neuropharmacology%22%5BJournal%5D)">Ivermectin reduces alcohol intake and preference in mice.</a> Neuropharmacology. 63, 190-201 (2012).</li>
<li>Hoggatt, A. F., Hoggatt, J., Honerlaw, M., Pelus, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+spoonful+of+sugar+helps+the+medicine+go+down%3A+a+novel+technique+to+improve+oral+gavage+in+mice%5BTitle%5D)+AND+%22J+Am+Assoc+Lab+Anim+Sci%22%5BJournal%5D)">A spoonful of sugar helps the medicine go down: a novel technique to improve oral gavage in mice.</a> J Am Assoc Lab Anim Sci. 49, 329-334 (2010).</li>
<li>Yardley, M. M., Huynh, N., Rodgers, K. E., Alkana, R. L., Davies, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Oral+delivery+of+ivermectin+using+a+fast+dissolving+oral+film%3A+implications+for+repurposing+ivermectin+as+a+pharmacotherapy+for+alcohol+use+disorder%5BTitle%5D)+AND+%22Alcohol%22%5BJournal%5D)">Oral delivery of ivermectin using a fast dissolving oral film: implications for repurposing ivermectin as a pharmacotherapy for alcohol use disorder.</a> Alcohol. 49 (6), 553-559 (2015).</li>
</ol>

DD已经申请了专利作为这个方法的共同发明人，并有兴趣与科学委员会分享这一方法，使这项技术众所周知的，随时可用于慢性动物试验（ 在实验动物药物活性成分的口服给药使用Fast-溶解口服电影 （戴维斯，共同发明人，专利申请提交2014年6月23日）。 没有其他竞争经济利益的说明。

口管饲法是与导致潜在的损害的数据收集和动物减员1的高速率许多并发症。此处的口服药物递送的一个简单的方法被引入，通过该小鼠（和潜在的其他动物）可容易且可靠地通过口服溶解条（ODS）消耗的首选药物。值得注意的是，使用这种方法的代表安全，方便，和人性化的替代口服管饲法。 其他流动资产替代口服灌胃，虽然有点希望的，与该妨碍他们覆盖了全方?...

为了使药物从临床前（动物试验）成功翻译到临床发展，一系列的明确定义，急性和慢性的药理学和毒理学研究需要在动物模型中也可以执行使用管理的预期临床路径（这是通常口服途径）。为了实现这个目标，最临床前研究目前利用给定的口服管饲法程序，该方法在测试化合物对动物的一致和精确的递送的效果。然而，在许多情况下，经口管饲法不能很好被动物耐受，越来越多的证据表明，该方法是用应力感应1的显著量相关联。 这是在用于需要长期的临床前研究慢性终身的条件下，如治疗的发展尤其如此与的情况下，但不限于，几乎每一个神经精神障碍。对于插件tance，在阿尔茨海默病的转基因小鼠模型，最近建议，强饲法本身可以由于加药引起的应力2混淆的实验结果。同样地，在酒精消费的小鼠模型中，我们的实验室未发表的研究结果已经发现，强饲管的重复插入 - 在其本身和 - 可以显著酒精摄入的水平减少到危及实验的完整性的点范例（ 见图1）。 定与口腔管饲过程相关联的上述限制，相当大的努力已投入朝着显影临床前口服药物递送的新方法。当前备选的方法包括掺入试验化合物成花生酱的混合物3，凝胶状模具4-5，巧克力小球6，饮用水7和晶片饼干8，所有这些都是associ有不同程度的问题，包括无法ated在动物模型可靠地使用，缺乏通过试验化合物的摄取的被测试受试者或风味个人偏好，使药物不易消耗9。 本文所介绍的过程描述了在其中需要的药物掺入调味，口腔溶解条（ODS），可以很容易地和很容易地被用于口服施用测试化合物对测试动物的方法。本文侧重于展示利用老鼠进行的ODS方法的有效性。然而，没有理由认为同样的方法将不会也有在其他啮齿动物，以及较大的哺乳动物受试者是有用的。临床上，使用消耗臭氧层物质的开始在儿童和老年患者被采纳，以此来克服吞咽困难10。我们建议，消耗臭氧层物质，也可以成功地在临床前药物研究计划作为一种安全，方便使用和人道的替代口服灌胃。

<table><tbody><tr><td>Orally Dissolving Strip&amp;nbsp;</td><td>Cure Pharmaceutical</td><td></td><td>Available upon special request. Alternatively, ODS may also be prepared in-house.</td></tr><tr><td>Gavage Feeding Needle</td><td>VWR</td><td>7912</td><td>Our rodent studies utilized a 18 gauge feeding needle. This size may need to be adjusted for use in other mammilian species.</td></tr><tr><td>Sucrose</td><td>Sigma Aldrich</td><td>S0389-500G</td><td></td></tr></tbody></table>

utilizing an orally dissolving strip for pharmacological and toxicological studies: a simple and humane alternative to oral gavage for animals

之前在人类中测试新的治疗，短期和长期的临床前（ 即动物），重复的药理和毒理试验是必需的。在大多数情况下，给药的优选途径是通过口服给药。在当前时刻，口服递送是使用口服管饲法过程，部分是因为它可以实现在动物模型一致和精确的定量给料大多完成。虽然这种方法是公认它确实有并发症，可能导致动物的高损耗率。为此，这里所介绍的过程描述，可以简单地呈现给测试动物在那里，然后迅速采取与替代，其中所希望的药物被掺入一个促味剂，口腔溶解条（ODS）的经口管饲法被检者的最小操纵。在此，我们证明，使用消耗臭氧层物质的方法临床前，口服给药代表了安全，便捷，人性化和阿尔特rnative口腔灌胃。

在下面的代表调查，社交饮酒是使用24小时双瓶选择（TBC）模式如前所述15建模。简言之，将小鼠获得的溶液两瓶，其中一个含有水，另10％（体积/体积）乙醇溶液中。受试者被随后分配到药物处理组，使得平均10E（10％乙醇/ 90％水体积/体积）的摄入量是跨组相似。 图1示出了当使用一个管饲车辆口服偏好...

Watch this Scientific Journal Video about Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals at JoVE.com

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals

以下方案描述了使用代替更常用的经口管饲法口服溶解条（ODS）慢性口服药物给药的新方法。我们表明，使用消耗臭氧层物质的方法临床前，口服给药代表了安全，方便，和人性化的替代口服灌胃。

利用一种口腔溶解地带的药理毒理研究:一个简单的和人道的替代口服灌胃动物

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is ...

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JoVE Journal

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12.7K 次观看.  University of Southern California School of Pharmacy. 以下方案描述了使用代替更常用的经口管饲法口服溶解条（ODS）慢性口服药物给药的新方法。我们表明，使用消耗臭氧层物质的方法临床前，口服给药代表了安全，方便，和人性化的替代口服灌胃。 

视频: Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

一种新的方法为评估味质的实验室大鼠的补强性能：操作性口腔自我管理

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

科研

行为学

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

The recently introduced microphysiological systems (MPS) cultivating human organoids are expected to perform better than animals in the preclinical tests phase of drug developing process because they are genetically human and recapitulate the interplay among tissues. In this study, the human intestinal barrier (emulated by a co-culture of Caco-2 and HT-29 cells) and the liver equivalent (emulated by spheroids made of differentiated HepaRG cells and human hepatic stellate cells) were integrated into a two-organ chip (2-OC) microfluidic device to assess some acetaminophen (APAP) pharmacokinetic (PK) and toxicological properties. The MPS had three assemblies: Intestine only 2-OC, Liver only 2-OC, and Intestine/Liver 2-OC with the same media perfusing both organoids. For PK assessments, we dosed the APAP in the media at preset timepoints after administering it either over the intestinal barrier (emulating the oral route) or in the media (emulating the intravenous route), at 12 &#181;M and 2 &#181;M respectively. The media samples were analyzed by reversed-phase high-pressure liquid chromatography (HPLC). Organoids were analyzed for gene expression, for TEER values, for protein expression and activity, and then collected, fixed, and submitted to a set of morphological evaluations. The MTT technique performed well in assessing the organoid viability, but the high content analyses (HCA) were able to detect very early toxic events in response to APAP treatment. We verified that the media flow does not significantly affect the APAP absorption whereas it significantly improves the liver equivalent functionality. The APAP human intestinal absorption and hepatic metabolism could be emulated in the MPS. The association between MPS data and in silico modeling has great potential to improve the predictability of the in vitro methods and provide better accuracy than animal models in pharmacokinetic and toxicological studies.

We exposed a microphysiological system (MPS) with intestine and liver organoids to acetaminophen (APAP). This article describes the methods for organoid production and APAP pharmacokinetic and toxicological property assessments in the MPS. It also describes the tissue functionality analyses necessary to validate the results.

药物药代动力学和毒理学评估的肠道/肝脏微生理系统

The recently introduced microphysiological systems (MPS) cultivating human organoids are expected to perform better than animals in the preclinical tests ...

化学

<meta charset="utf8"></head><body>使用微量移液器引导的给药减轻研究动物的压力

Use of Micropipette-Guided Drug Administration as an Alternative Method to Oral Gavage in Rodent Models

Oral gavage (OG) with the use of a cannula attached to a syringe is one of the most common methods used to deliver precise dosing of compounds to the stomach of research animals. Unfortunately, this method comes with difficulties for both the operator and the research animal. Studies have shown that OG may lead to complications, including esophagitis, perforation of the esophagus, and inadvertent tracheal drug administration. In addition, OG is associated with increased plasma and fecal corticosterone levels (due to stress), altered blood pressure, and increased heart rate, which could negatively influence or bias study results. A previously developed alternative method termed micropipette-guided drug administration (MDA) incentivizes the animal to consume treatments readily in a minimally invasive manner. Herein, we present examples of the use of the MDA technique with treatments reconstituted in different vehicles and demonstrate effective delivery of the varied treatments to multiple different mouse strains. We further demonstrate that MDA is a technique that decreases the timing and invasiveness of drug administration and does not affect the gut microbiome composition as assessed by quantitative analysis of core gut microbial species. Overall, MDA may offer a less stressful and effective alternative to OG.

<meta charset="utf8"></head><body>在啮齿动物模型中使用微量移液器引导给药作为口服灌胃的替代方法

Here, we describe micropipette-guided drug administration (MDA) as an alternative method to oral gavage that incentivizes the research animal to ingest treatments readily with minimal stress and discomfort.

在啮齿动物模型中使用微量移液器引导给药作为口服灌胃的替代方法

Oral gavage (OG) with the use of a cannula attached to a syringe is one of the most common methods used to deliver precise dosing of compounds to the ...

癌症研究

Manual Restraint and Common Compound Administration Routes in Mice and Rats

Being able to safely and effectively restrain mice and rats is an important part of conducting research. Working confidently and humanely with mice and rats requires a basic competency in handling and restraint methods. This article will present the basic principles required to safely handle animals. One-handed, two-handed, and restraint with specially designed restraint objects will be illustrated. Often, another part of the research or testing use of animals is the effective administration of compounds to mice and rats. Although there are a large number of possible administration routes (limited only by the size and organs of the animal), most are not used regularly in research. This video will illustrate several of the more common routes, including intravenous, intramuscular, subcutaneous, and oral gavage. The goal of this article is to expose a viewer unfamiliar with these techniques to basic restraint and substance administration routes. This video does not replace required hands-on training at your facility, but is meant to augment and supplement that training.

Working safely and humanely with research rodents requires a core competency in handling and restraint methods. This article will present the basic principles required to safely handle and effectively administer compounds to mice and rats.

手动约束和常见的化合物在小鼠和大鼠的给药途径

Being able to safely and effectively restrain mice and rats is an important part of conducting research.  Working confidently and humanely with mice and ...

生物学

Oral Intubation of Adult Zebrafish: A Model for Evaluating Intestinal Uptake of Bioactive Compounds

Most pathogens invade organisms through their mucosa. This is particularly true in fish as they are continuously exposed to a microbial-rich water environment. Developing effective methods for oral delivery of immunostimulants or vaccines, which activate the immune system against infectious diseases, is highly desirable. In devising prophylactic tools, good experimental models are needed to test their performance. Here, we show a method for oral intubation of adult zebrafish and a set of procedures to dissect and prepare the intestine for cytometry, confocal microscopy and quantitative polymerase chain reaction (qPCR) analysis. With this protocol, we can precisely administer volumes up to 50 &#181;L to fish weighing approximately 1 g simply and quickly, without harming the animals. This method allows us to explore the direct in vivo uptake of fluorescently labelled compounds by the intestinal mucosa and the immunomodulatory capacity of such biologics at the local site after intubation. By combining downstream methods such as flow cytometry, histology, qPCR and confocal microscopy of the intestinal tissue, we can understand how immunostimulants or vaccines are able to cross the intestinal mucosal barriers, pass through the lamina propria, and reach the muscle, exerting an effect on the intestinal mucosal immune system. The model could be used to test candidate oral prophylactics and delivery systems or the local effect of any orally administered bioactive compound.

The protocol describes intubating adult zebrafish with a biologic; then dissecting and preparing the intestine for cytometry, confocal microscopy and qPCR. This method allows administration of bioactive compounds to monitor intestinal uptake and the local immune stimulus evoked. It&#160;is relevant for testing the intestinal dynamics of oral prophylactics.

成年斑马鱼的口服插管: 一种评价生物活性化合物肠道吸收的模型

Most pathogens invade organisms through their mucosa. This is particularly true in fish as they are continuously exposed to a microbial-rich water ...

免疫与感染

Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered. This precludes conducting early feasibility studies as insufficient drug is available at the research or early development stage to support the dose delivery requirements for conventional aerosol delivery systems. When designing an aerosol drug product, aerodynamic performance can relate directly to delivery efficiency and efficacy. Dispersion of powder into an aerosol requires energy input sufficient to overcome interparticulate forces, and particle engineering approaches can substantially improve aerosol performance. We have developed a dispersion system (dosator) which can aerosolize engineered dry powder aerosols efficiently for the purpose of direct pulmonary insufflation, dispersion into an exposure system or generation for analytical purposes.

During development of drugs for pulmonary delivery, it is necessary to evaluate pharmacokinetics and efficacy in an animal model. We present a method to build a disposable aerosol dispersion system from of-the-shelf components that can be used to administer intrapulmonary dry powder aerosol to rodents.

一次性充填机对治疗药物的肺吹入小动物

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver ...

医学

Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease. In contrast to asthma, there are few effective therapies for COPD. An estimated 10% of the population has COPD and the trend in death rates is increasing for COPD while decreasing for other major diseases. Although developing drugs for inhaled delivery is challenging, the nose-only inhalation unit enables direct delivery of novel drugs to the lung of rodents for pre-clinical efficacy and safety/toxicology studies. Inhaled drug delivery has multiple advantages for respiratory diseases, where high concentration in the lung improves efficacy and minimizes systemic side effects. Inhaled corticosteroids and bronchodilators benefit from these advantages and inhaled delivery may also hold potential for future biologic therapies. The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs of rodents, key data required before initiating clinical development.

The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs; key data enabling clinical inhaled drug development.

干粉和药品的雾化吸入气雾剂递送小鼠使用鼻只曝光系统

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and ...

Preparation Of Gushukang (GSK) Granules for In Vivo and In Vitro Experiments

Traditional Chinese herbal medicine plays a role as an alternative method in treating many diseases, such as postmenopausal osteoporosis (POP). Gushukang (GSK) granules, a marketed prescription in China, have bone-protective effects in treating POP. Before administration to the body, one standard preparation procedure is commonly required, which aims to promote the release of active constituents from raw herbs and enhance the pharmacological effects as well as therapeutic outcomes. This study proposes a detailed protocol for using GSK granules in in vivo and in vitro experimental assays. The authors first provide a detailed protocol to calculate the animal-appropriate dosages of granules for in vivo investigation: weighing, dissolving, storage, and administration. Second, this article describes protocols for micro-CT scanning and the measurement of bone parameters. Sample preparation, protocols for running the micro-CT machine and quantification of bone parameters were evaluated. Third, serum-containing GSK granules are prepared, and drug-containing serum is extracted for in vitro osteoclastogenesis and osteoblastogenesis. GSK granules were intragastrically administered twice per day to rats for three consecutive days. Blood was then collected, centrifuged, inactivated, and filtered. Finally, serum was diluted and used for performing osteoclastogenesis and osteoblastogenesis. The protocol described here can be considered a reference for pharmacological investigations of herbal prescription medicines, such as granules.

Preparation Of Gushukang GSK Granules for In Vivo and In Vitro Experiments

This article provides a detailed protocol for preparing a working solution of Gushukang granules for animal studies and GSK granule containing serum for in vitro experiments. This protocol can be applied to pharmacological investigations of herbal medicines as well as prescriptions for both in vivo and in vitro experiments.

古树康 (GSK) 颗粒的制备,用于 Vivo 和体外实验

Traditional Chinese herbal medicine plays a role as an alternative method in treating many diseases, such as postmenopausal osteoporosis (POP). Gushukang ...

利用一种口腔溶解地带的药理毒理研究:一个简单的和人道的替代口服灌胃动物

摘要

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药物药代动力学和毒理学评估的肠道/肝脏微生理系统

在啮齿动物模型中使用微量移液器引导给药作为口服灌胃的替代方法

在啮齿动物模型中使用微量移液器引导给药作为口服灌胃的替代方法

在啮齿动物模型中使用微量移液器引导给药作为口服灌胃的替代方法

手动约束和常见的化合物在小鼠和大鼠的给药途径

成年斑马鱼的口服插管: 一种评价生物活性化合物肠道吸收的模型

一次性充填机对治疗药物的肺吹入小动物

干粉和药品的雾化吸入气雾剂递送小鼠使用鼻只曝光系统

古树康 (GSK) 颗粒的制备,用于 Vivo 和体外实验