Name: intratracheal administration of dry powder formulation in mice
Uploaded: 2020-07-25T15:00:00.000+00:00
Duration: 7 min 55 s
Description: Watch this Scientific Journal Video about Intratracheal Administration of Dry Powder Formulation in Mice at JoVE.com

作者要感谢李光耀先生、梁振英先生和苏华莱士先生，感谢他们在制造光源和粉末充气器方面给予的善意协助:和动物成像援助的学院核心设施。这项工作得到了香港研究资助委员会（17300319）的支持。

本研究的实验已获香港大学活体动物教学及研究委员会（CULATR）批准。本研究使用喷雾冷冻干燥（SFD）制备的干粉配方，其中含有0.5%的红素酶信使RNA（mRNA）、5%的合成肽PEG12KL4和94.5%的曼尼托（w/w），用于演示肺16中的mRNA表达。SFD 粉末的质中空气动力学直径 （MMAD） 为 2.4μm。喷雾干燥（SD）曼尼托粉用于研究粉末分散16中使用的空气量的影响。SD 粉末的 MMAD 为 1.5μm。
1. 制造干粉窒息器和装载干粉
<ol><li>（可选）中和干粉（小瓶中）和 200 μL 非滤光圆凝胶加载移液器尖端的静电。根据制造商的指示，使用防静电枪或与除离子功能的平衡。</li>
	<li>准备一张尺寸约为 4 厘米 x 4 厘米的称重纸。将纸张对角线折叠成两半，然后展开。</li>
	<li>称重纸上重1-2毫克干粉。</li>
	<li>通过更宽的开口用粉末填充凝胶加载移液器尖端。轻轻敲击以包装粉末，直到粉末在尖端狭窄端附近形成松散的聚集物（图1A）。避免将粉末包装得太紧，因为它可能会阻碍粉末的分散。</li>
	<li>通过三向塞孔（图 1B ）将装粉尖连接到1mL 注射器。注射器的大小可以根据用于分散粉末的空气量而改变。连接期间垂直握住尖端和注射器，以防止粉末溢出。如果不立即执行管理，使用寄生胶片密封尖端的开口，并暂时在适当条件下存储，直到管理。</li>
</ol>2. 内存设备的制造
<ol><li>光源 （图2）<ol>
<li>用发光二极管 （LED） 手电筒和直径为 0.8-1 mm 的柔性光纤准备定制光源。</li>
		<li>用手钻或钻头在 LED 手电筒的透明透镜上制作一个中心孔，使光纤几乎无法通过。</li>
		<li>通过孔插入光纤。打开 LED 手电筒，调整插入的位置和深度，以获得光纤另一端的最大亮度。</li>
		<li>将光纤与透明环氧胶粘合到位。</li>
	</ol>
</li>
	<li>指导犬 （图 3）<ol>
<li>拿一个1mL塑料巴斯德移液器（图3A），把移液器保持在两端。</li>
		<li>使用酒精灯（或实验室中的其他热源，如邦森燃烧器）将酒精灯放在火焰上方 5-10 厘米处加热移液器中间（图 3B）。旋转移液器，以确保均匀加热。</li>
		<li>当塑料变软变形时，将移离火焰的移开移动器，轻轻伸展移液器。</li>
		<li>用一把剪刀将中间拉伸的移液器切成 A 部分和 B 部分（图 3C-E）。使用第 A 部分作为精细的尖端移液器，将 B 部分用作引导管。为了增加成功与引导管管交配的机会，在 B 部分（图 3F）的末尾制作一个斜面（不太锋利，这可能会增加伤害动物的风险）。当将 200 μL 凝胶加载移液器尖端（用于粉末装载）插入导管时，应将管子突出 1-2 mm。 注:具有适当尺寸（内部和外部直径）进行插管的导管（B部分）内部和外部针头内可容纳21根针头，同时也可以放入17号针内。在拉伸移液管时可能需要多次尝试才能达到适当的尺寸。</li>
		<li>（可选）:在导管的较宽端切开一个小开口，使其更加灵活，以便更容易保持光纤（图3F）。此开口还允许安装用于液体气溶胶管理的微喷雾器。</li>
	</ol>
</li>
</ol>3. 灌引
<ol><li>通过腹腔内注射将小鼠（BALB/c，7-9周）与氯胺酮（100毫克/千克）和西拉津（10毫克/千克）麻醉。</li>
	<li>准备一个用玻璃制成的平台，并将其安装到带夹子的支架上（图4A）。将麻醉鼠标放在平台上（倾斜度约为 60° 时）置于超平位置。平台的高度和倾斜角度可以通过支架上的夹子位置进行调整。</li>
	<li>将鼠标的切口钩在尼龙牙线上（图4B）。暂停鼠标。用胶带或橡皮筋固定鼠标的位置。</li>
	<li>在导引管打开时，将光纤插入导管中，然后用光纤水平尖进行插管。打开 LED 手电筒进行照明。</li>
	<li>用一对钳子轻轻伸出老鼠的舌头，露出它的气管。</li>
	<li>用另一只手用光纤将导管握住。通过口腔插入它们。通过光纤的照明，气管的开口可以可视化为声带之间的孔。</li>
	<li>将引导罐的斜面对准开口的中线（图 5A）。通过将导管的最佳尖端瞄准气管开口，用光纤轻轻地将引导管插入气管。</li>
	<li>入管后，迅速取出光纤，将导管留在气管内（图5B）。应观察正常的呼吸。</li>
	<li>在引导管的开口处握住细尖移液器（A部分），将少量的空气（约0.2 mL）注入小鼠的肺部。小鼠胸部的轻微膨胀表示适当的内分。在粉末管理之前取出细尖移液器。</li>
</ol>4. 粉末管理
<ol><li>按住与第 1.5 步中描述的注射器相连的粉末加载尖端。确保注射器和尖端之间的气流断开。</li>
	<li>向后拉注射器柱塞以提取 0.6 mL 的空气。 注:用于分散粉末的空气体积取决于粉末的特性和所装粉量。结果部分进一步描述了这一点。</li>
	<li>转动三向塞孔的阀门，将注射器和粉末加载尖端之间的气流连接起来。</li>
	<li>将装有粉末的尖端插入已放置在鼠标气管中的导管（图 5C）中。握住引导管，用力推注射器柱塞，以连续动作将粉末分散为气溶胶进入肺部。 注意:设备的任何前向运动应最小化，以避免伤害动物。</li>
	<li>取出尖端并检查尖端内的粉末是否已清空。如果没有，重复步骤 4.1 到 4.4。 注意:如果粉末因过度敲击而包装过于紧密，则可能无法正确分散。</li>
	<li>管理完成后，从气管中取出引导管。</li>
	<li>允许鼠标通过水平定位在一个超平位置，其舌头半突出，以避免气道的封锁恢复。</li>
</ol>

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作者没有利益冲突要披露。

本文介绍了用于干粉窒息和体内插管的定制设备。在粉末装载步骤中，干粉末被加载到 200 μL 凝胶加载移液器尖端。重要的是轻轻敲击尖端，使粉末在尖端的狭窄端松散包装。但是，如果粉末包装太紧，它们会卡在尖端，无法正确分散。建议中和粉末和移液器尖端的静电荷，以方便粉末装载，特别是低密度和低相对湿度的粉末。引导管是设备的关键部件。它用于促进将装有粉末的移液器尖端插入?...

肺病的施政途径为局部和系统行动提供治疗提供各种好处。对于肺病的治疗，可以通过肺分娩实现高局部药物浓度，从而减少所需剂量，降低全身副作用的发生率。此外，肺部相对较低的酶活性可以减少过早的药物代谢。肺部也有效地吸收药物的全身作用，由于大和良好的灌注表面积，极薄的上皮细胞层和肺毛细血管1的高血量。
吸入干粉配方已被广泛研究，用于预防和治疗各种疾病，如哮喘，慢性阻塞性肺病，糖尿病和肺疫苗接种2，3，4。固体状态下的药物通常比液体形式更稳定，干粉吸入器比雾化器5、6更便携、更方便用户。在开发吸入干粉配方时，需要在肺管理7后，在药物前动物模型中评估其安全性、药效和疗效。与能主动吸入干粉的人类不同，肺向小动物输送干粉具有挑战性。有必要建立一个有效的协议，将干粉送到动物的肺部。
老鼠被广泛用作研究动物模型，因为它们经济，繁殖良好。它们也易于处理，许多疾病模型都已建立起来。给小鼠肺部施用干粉有两种主要方法:吸入和体内管理。为了吸入，小鼠被放置在全身或鼻子专用室，其中干粉被气溶胶化，动物呼吸气溶胶没有安定8，9。设备昂贵，药品输送效率低。虽然全身腔在技术上可能不那么具有挑战性，但仅鼻腔暴露室可以最大限度地减少药物暴露在身体表面。无论如何，仍然很难精确控制和确定交付到肺部的剂量。干粉主要沉积在鼻咽部位，其中粘膜清除突出10。此外，在管理过程中，室内老鼠承受着巨大的压力，因为它们受到限制，得不到食物和水的供应。对于体内管理，它通常是指将物质直接引入气管。有两种不同的技术来实现这一点:气管切除术和骨质管内分。前者需要外科手术，使气管切口，这是侵入性的，很少用于粉末管理。这里只描述了第二种技术。与吸入法相比，体内输病是小鼠肺输配的常用方法，因为其输送效率高，药物损失最小。这是一种简单快捷的方法，可在几毫克内精确地将少量粉末输送到鼠标。虽然小鼠在解剖学和生理上与人类不同，在插管过程中需要麻醉，但内科管理绕过上呼吸道，为评估干粉配方的生物活动（如肺吸收、生物利用和治疗效果）提供了更有效的方法。
要在内经管理干粉，必须插管小鼠，这可能具有挑战性。本文介绍了定制干粉灌装器和管内装置的制造情况。演示了在小鼠肺部进行干燥粉末的灌接和窒息过程。

<table><tbody><tr><td>BALB/c mouse</td><td></td><td></td><td>Female; 7-9 weeks old; Body weight 20-25 g</td></tr><tr><td>CleanCap Firefly Luciferase mRNA</td><td>TriLink Biotechnology</td><td>L-7602</td><td></td></tr><tr><td>Dry Powder Insufflator</td><td>PennCentury</td><td>Model DP-4M</td><td></td></tr><tr><td>Ketamine 10%</td><td>Alfasan International B.V.</td><td>NA</td><td></td></tr><tr><td>Light emitting diode (LED) torch</td><td>Unilite Internation</td><td>PS-K1</td><td></td></tr><tr><td>Mannitol (Pearlitol 160C)</td><td>Roquette</td><td>450001</td><td></td></tr><tr><td>Non-filter round gel loading pipette tip (200 &amp;micro;L)</td><td>Labcon</td><td>1034-800-000</td><td></td></tr><tr><td>Nylon floss</td><td>Reach</td><td>30017050</td><td></td></tr><tr><td>One milliliter syringe without needle</td><td>Terumo</td><td>SS-01T</td><td></td></tr><tr><td>Optical fibre</td><td>Fibre Data</td><td>OMPF1000</td><td></td></tr><tr><td>PEG12KL4 peptide</td><td>EZ Biolab</td><td></td><td>(PEG12)-KLLLLKLLLLKLLLLKLLLLK-NH2</td></tr><tr><td>Plastic Pasteur fine tip pipette</td><td>Alpha Labotatories</td><td>LW4061</td><td></td></tr><tr><td>Three-way stopcock</td><td>Braun</td><td>D201</td><td></td></tr><tr><td>Xylazine 2%</td><td>Alfasan International B.V.</td><td>NA</td><td></td></tr><tr><td>Zerostat 3 anti-static gun</td><td>MILTY</td><td>5036694022153</td><td></td></tr></tbody></table>

intratracheal administration of dry powder formulation in mice

在开发可吸入干粉配方时，必须评估其在前层动物模型中的生物活动。本文介绍了一种在小鼠体内输送干粉制剂的非侵入性方法。提供由 200 μL 凝胶装载移液器尖端组成的干粉装装置，通过三向塞孔连接到 1 mL 注射器。少量干粉（1-2毫克）被装入移液器尖端，并在注射器中通过0.6毫升的空气分散。由于移液器尖端是一次性的，价格低廉，因此可以提前将不同的干粉配方加载到不同的提示中。在同一动物实验中，无需设备清洁和剂量补充，即可评估各种配方，从而节省时间并消除残留粉末交叉污染的风险。粉末分散的程度可以通过移液器尖端残留的粉末量来检查。包括一个带有定制光源和导引管的鼠标内导管协议。适当的插管是影响干粉配方在健康内输送到小鼠深肺区域的关键因素之一。

当使用干粉充气器将粉末气溶胶输送到动物的肺部时，所使用的空气量至关重要，因为它会影响粉末的安全性以及粉末分散效率。为了优化该方法，使用不同体积的空气（0.3 mL、0.6 mL 和 1.0 mL）来分散干粉（1 毫克喷雾干曼尼托），并在给药后监测小鼠的重量 48 小时（图 6）。使用0.3 mL和0.6 mL的空气不会导致小鼠在施用后体重减轻至48小时。将粉末与 1 mL 空气分散，在 24 小时...

Watch this Scientific Journal Video about Intratracheal Administration of Dry Powder Formulation in Mice at JoVE.com

Intratracheal Administration of Dry Powder Formulation in Mice

吸入干粉配方在治疗呼吸系统疾病方面有很大的潜力。在进入人类研究之前，有必要在前科研究中评估干粉配方的功效。提出了一种简单而非侵入性的方法，通过体外路线对小鼠的干粉进行管理。

小鼠干粉配方的内经管理

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...

intratracheal-administration-of-dry-powder-formulation-in-mice

Research

JoVE Journal

Medicine

9.9K 次观看.  The University of Hong Kong. 吸入干粉配方在治疗呼吸系统疾病方面有很大的潜力。在进入人类研究之前，有必要在前科研究中评估干粉配方的功效。提出了一种简单而非侵入性的方法，通过体外路线对小鼠的干粉进行管理。

视频: Intratracheal Administration of Dry Powder Formulation in Mice

Non-surgical Intratracheal Instillation of Mice with Analysis of Lungs and Lung Draining Lymph Nodes by Flow Cytometry

Phagocytic cells such as alveolar macrophages and lung dendritic cells (LDCs) continuously sample antigens from the alveolar spaces in the 
lungs. LDCs, in particular, are known to migrate to the lung draining lymph nodes (LDLNs) where they present inhaled antigens to T cells initiating an 
appropriate immune response to a variety of immunogens1,2. To model interactions between the lungs and airborne antigens in mice, antigens can be 
administered intranasally1,3,4, intratracheally5 or as aerosols6. Delivery by each route involves distinct technical skills and limitations that need to be 
considered before designing an experiment. For example, intranasal and aerosolized exposure delivers antigens to both the lungs and the upper respiratory 
tract. Hence antigens can access the nasal associated lymphoid tissue (NALT)7, potentially complicating interpretation of the results. In addition, swallowing, 
sneezing and the breathing rate of the mouse may also lead to inconsistencies in the doses delivered. Although the involvement of the upper respiratory tract may 
be preferred for some studies, it can complicate experiments focusing on events specifically initiated in the lungs. In this setting, the intratracheal (i.t) 
route is preferable as it delivers test materials directly into the lungs and bypasses the NALT. Many i.t injection protocols involve either blind intubation of the 
trachea through the oral cavity or surgical exposure of the trachea to access the lungs. Herein, we describe a simple, consistent, non-surgical method for i.t 
instillation. The opening of the trachea is visualized using a laryngoscope and a bent gavage needle is then inserted directly into the trachea to deliver the 
innoculum. We also describe procedures for harvesting and processing of LDLNs and lungs for analysis of antigen trafficking by flow cytometry.

We illustrate non-surgical delivery of test materials into the lungs of anesthetized mice via the trachea. This method permits lung exposure to bacterial and viral pathogens, cytokines, antibodies, beads, chemicals, or dyes. We further describe harvesting and processing of lungs and lung draining lymph nodes (LDLNs) for flow cytometry.

非手术治疗的小鼠气管内滴入肺和肺淋巴结流式细胞仪分析

Phagocytic cells such as alveolar macrophages and lung dendritic cells (LDCs) continuously sample antigens from the alveolar spaces in the 
lungs. LDCs, ...

科研

免疫与感染

Direct Tracheal Instillation of Solutes into Mouse Lung

Intratracheal instillations deliver solutes directly into the lungs. This procedure targets the delivery of the instillate into the distal regions of the lung, and is therefore often incorporated in studies aimed at studying alveoli. We provide a detailed survival protocol for performing intratracheal instillations in mice. Using this approach, one can target delivery of test solutes or solids (such as lung therapeutics, surfactants, viruses, and small oligonucleotides) into the distal lung. Tracheal instillations may be the preferred methodology, over inhalation protocols that may primarily target the upper respiratory tract and possibly expose the investigator to potentially hazardous substances. Additionally, in using the tracheal instillation protocol, animals can fully recover from the non-invasive procedure. This allows for making subsequent physiological measurements on test animals, or reinstallation using the same animal. The amount of instillate introduced into the lung must be carefully determined and osmotically balanced to ensure animal recovery. Typically, 30-75 &mu;L instillate volume can be introduced into mouse lung.

Intratracheal instillations deliver solutes directly into the lungs. This procedure targets the delivery of the instillate into the distal regions of the lung, and is therefore often incorporated in studies aimed at studying alveoli. We provide a detailed survival protocol for performing intratracheal instillations in mice.

溶质直接气管滴入小鼠肺

Intratracheal instillations deliver solutes directly into the lungs.  This procedure targets the delivery of the instillate into the distal regions of the ...

生物学

Intubation-mediated Intratracheal (IMIT) Instillation: A Noninvasive, Lung-specific Delivery System

Respiratory disease studies typically involve the use of murine models as surrogate systems. However, there are significant physiologic differences between the murine and human respiratory systems, especially in their upper respiratory tracts (URT). In some models, these differences in the murine nasal cavity can have a significant impact on disease progression and presentation in the lower respiratory tract (LRT) when using intranasal instillation techniques, potentially limiting the usefulness of the mouse model to study these diseases. For these reasons, it would be advantageous to develop a technique to instill bacteria directly into the mouse lungs in order to study LRT disease in the absence of involvement of the URT. We have termed this lung specific delivery technique intubation-mediated intratracheal (IMIT) instillation. This noninvasive technique minimizes the potential for instillation into the bloodstream, which can occur during more invasive traditional surgical intratracheal infection approaches, and limits the possibility of incidental digestive tract delivery. IMIT is a two-step process in which mice are first intubated, with an intermediate step to ensure correct catheter placement into the trachea, followed by insertion of a blunt needle into the catheter to mediate direct delivery of bacteria into the lung. This approach facilitates a &#62;98% efficacy of delivery into the lungs with excellent distribution of reagent throughout the lung. Thus, IMIT represents a novel approach to study LRT disease and therapeutic delivery directly into the lung, improving upon the ability to use mice as surrogates to study human respiratory disease. Furthermore, the accuracy and reproducibility of this delivery system also makes it amenable to Good Laboratory Practice Standards (GLPS), as well as delivery of a wide range of reagents which require high efficiency delivery to the lung.

Intubation-mediated Intratracheal IMIT Instillation: A Noninvasive, Lung-specific Delivery System

Intubation-mediated intratracheal (IMIT) instillation of reagents is an excellent, noninvasive method for studying respiratory disease, as well as a method for instilling therapeutic reagents directly into the lung. It is a rapid and highly reproducible method which is suitable for preclinical testing.

插管介导气管内（IMIT）灌输:一种无创，龙专用输送系统

Respiratory disease studies typically involve the use of murine models as surrogate systems. However, there are significant physiologic differences ...

医学

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity is a commonly used model to study both acute lung injury and fibrosis, and multiple methods have been developed for administering bleomycin (and other toxic agents) into the lungs. However, many of these approaches, such as transtracheal instillation, have inherent drawbacks, including the need for strong anesthetics and survival surgery. This paper reports a quick, reproducible method of intratracheal intubation that involves mild inhaled anesthesia, visualization of the trachea, and the use of a surrogate spirometer to confirm exposure. As a proof of concept, 8-12 week old C57BL/6 mice were administered either 2.0 U/kg of bleomycin or an equivalent volume of PBS, and both damage and fibrotic endpoints were measured post-exposure. This procedure allows researchers to treat a large cohort of mice in a relatively short period with little expense and minimal post-procedure care.

This article presents a rapid and simple method for administering bleomycin directly into the mouse trachea via intubation. Key advantages of this method are that it is highly reproducible, easy to master, and does not require specialized equipment or lengthy recovery times.

在小鼠气管插管快速的改进方法

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

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 ...

Direct Intrabronchial Administration to Improve the Selective Agent Deposition Within the Mouse Lung

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced pulmonary fibrosis.&#160; However, distribution of intratracheally-administered agents to the distal mouse lung is often asymmetric, with lung parenchymal concentrations increased in the smaller (but equally accessible) left lung of the mouse.&#160; Described in this report is a novel intrabronchial (IB) approach to cannulate the left and/or right lungs of living mice non-operatively.&#160; It is also demonstrated how this approach can be used to selectively administer agents to one lung or adapted (via dose-adjusted IB delivery) to improve the left-right symmetry of lung delivery of experimental agents, thereby improving models of diffuse lung disease such as bleomycin-induced pulmonary fibrosis.

Intratracheal (IT) administration of experimental agents in mice often results in asymmetric delivery to the distal lungs.&#160; In this report, we describe a direct intrabronchial (IB) approach to cannulate each lung in living mice non-operatively.&#160; This approach can be used to selectively administer agents to one lung or may be adapted to improve the symmetric agent delivery to both lungs.

直接注射内管理,改善小鼠肺内的选择性代理沉积

Intratracheal (IT) administration of experimental agents is an essential technique in murine models of diffuse lung diseases, such as bleomycin-induced ...

A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease

Treatment of neonatal rodent with drugs instilled directly into the trachea could serve as a valuable tool to study the impact of a locally administered drug. This has direct translational impact because surfactant and drugs are administered locally into the lungs. Though the literature has many publications describing minimally invasive transoral intubation of adult mice and rats in therapeutic experiments, this approach in neonatal rat pups is lacking. The small size of orotracheal region/pharynx in the pups makes visualization of laryngeal lumen (vocal cords) difficult, contributing to the variable success rate of intratracheal drug delivery. We hereby demonstrate effective oral intubation of neonatal rat pup - a technique that is non-traumatic and minimally-invasive, so that it can be used for serial administration of drugs. We used an operating otoscope with an illumination system and a magnifying lens to visualize the tracheal opening of the rat neonates. The drug is then instilled using a 1 mL syringe connected to a pipette tip. The accuracy of the delivery method was demonstrated using Evans blue dye administration. This method is easy to get trained in and could serve as an effective way to instill drugs into trachea. This method could also be used for administration of inoculum or agents to simulate disease conditions in animals and, also, for cell-based treatment strategies for various lung diseases.

This technique of instilling drugs directly into the trachea of neonatal rodents is important in studying the impact of locally administered drugs or biologicals on neonatal lung diseases. Additionally, this method can also be used for inducing lung injury in animal models.

一种新生儿啮齿动物气管内滴注药物治疗肺部疾病的微创方法

Treatment of neonatal rodent with drugs instilled directly into the trachea could serve as a valuable tool to study the impact of a locally administered ...

可定制的一次性给药器，用于将干粉气雾剂药物输送给小鼠

Disposable Dosators Intended for Dry Powder Delivery to Mice

Dry powder inhalers offer numerous advantages for delivering drugs to the lungs, including stable solid-state drug formulations, device portability, bolus metering and dosing, and a propellant-free dispersal mechanism. To develop pharmaceutical dry powder aerosol products, robust in vivo testing is essential. Typically, initial studies involve using a murine model for preliminary evaluation before conducting formal studies in larger animal species. However, a significant limitation in this approach is the lack of suitable device technology to accurately and reproducibly deliver dry powders to small animals, hindering such models&#39; utility. To address these challenges, disposable syringe dosators were developed specifically for intrapulmonary delivery of dry powders in doses appropriate for mice. These dosators load and deliver a predetermined amount of powder obtained from a uniform bulk density powder bed. This discrete control is achieved by inserting a blunt needle to a fixed depth (tamping) into the powder bed, removing a fixed quantity each time. Notably, this dosing pattern has proven effective for a range of spray-dried powders. In experiments involving four different model spray-dried powders, the dosators demonstrated the ability to achieve doses within the range of 30 to 1100 &#181;g. The achieved dose was influenced by factors such as the number of tamps, the size of the dosator needle, and the specific formulation used. One of the key benefits of these dosators is their ease of manufacturing, making them accessible and cost-effective for delivering dry powders to mice during initial proof-of-concept studies. The disposable nature of the dosators facilitates use in animal procedure rooms, where cleaning and refilling reusable systems and weighing materials is inconvenient. Thus, developing disposable syringe dosators has addressed a significant hurdle in murine dry powder delivery for proof-of-concept studies, enabling researchers to conduct more accurate and reproducible preliminary studies in small animal models for pulmonary drug delivery.

作者聚焦：开发一次性给药剂，用于小动物模型中干粉吸入器的临床前 测试 

Pharmaceutical dry powder development necessitates reliable in vivo testing, often using a murine model. Device technology for accurately and reproducibly delivering dry powder aerosols to mice is restricted. This study presents disposable dosators for pulmonary drug delivery at mouse-relevant doses, aiding initial proof-of-concept research.

用于将干粉输送给小鼠的一次性给药器

Dry powder inhalers offer numerous advantages for delivering drugs to the lungs, including stable solid-state drug formulations, device portability, bolus ...

小鼠干粉配方的内经管理

摘要

探索更多视频

此视频中的章节

非手术治疗的小鼠气管内滴入肺和肺淋巴结流式细胞仪分析

溶质直接气管滴入小鼠肺

插管介导气管内（IMIT）灌输:一种无创，龙专用输送系统

在小鼠气管插管快速的改进方法

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

直接注射内管理,改善小鼠肺内的选择性代理沉积

一种新生儿啮齿动物气管内滴注药物治疗肺部疾病的微创方法

用于将干粉输送给小鼠的一次性给药器

用于将干粉输送给小鼠的一次性给药器

用于将干粉输送给小鼠的一次性给药器