Name: disposable dosators for pulmonary insufflation of therapeutic agents to small animals
Uploaded: 2017-03-30T13:00:00.000+00:00
Duration: 4 min 22 s
Description: Watch this Scientific Journal Video about Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals at JoVE.com

Autores gostariam de agradecer a gentileza do Instituto Nacional de Alergia e Doenças Infecciosas para o financiamento para realizar esta pesquisa.

1. Preparação dos Componentes do doseadores <ol><li> Perfurar a parte inferior de um tubo de microcentrífuga de 0,5 ml de polipropileno por perfuração ou por simplesmente moer ou cortar o fundo com uma roda de esmeril ou uma tesoura afiada. Certifique-se de que o orifício está localizado no centro e é não mais do que 2 mm de diâmetro e não menos do que 1 mm de diâmetro (Figura 1). </li><li> Perfurar a parte superior do tubo de microcentrífuga. Utilizando uma broca # 22 (aproximadamente 4 mm de diâmetro), fazer um furo no centro da tampa. Isso resulta em um furo que vai encaixar uma seringa deslizamento-ponta (Figura 1). </li><li> Preparar as telas finas a serem inseridos nos tubos de microcentrífuga. Adicione telas de 304 pano de fio de aço inoxidável, de 60 x 60 mesh com um diâmetro de arame de 0,0045&quot; . Cortar as telas com recortes de estanho ou perfurar-los usando uma fieira com um diâmetro exterior de 5 mm (Figura 2). </li></ol> 2. Assembleia da doseadores <ol><li> Utilizando qualquer um dos fórceps ou a extremidade de uma agulha de ponta romba, inserir o ecrã para dentro do tubo de microcentrífuga e encaixá-lo na parte inferior de modo que cobre a abertura. Isto vai servir para suportar o pó antes da actuação. </li><li> Pressione encaixar a extremidade mais estreita da ponta de microcentrífuga para dentro da extremidade de uma agulha de ponta romba. Faça isso com a mão ou com uma prensa de bancada e um guia. Limpe suavemente a parte superior da agulha e da parte inferior do tubo com etanol para limpar as partes para garantir um ajuste apertado resiliente. </li></ol> 3. Encher o doseadores <ol><li> Usando uma microbalança analítica, tarar o dispositivo e carregar a quantidade desejada de pó para dentro do doseador. A massa de pó típico para dispersão varia de 1 a 10 mg. </li><li> Uma vez preenchido, ligue a parte superior do tubo de microcentrífuga com uma atribuição de algodão e um par de fórceps. Isso vai impedir que o pó de tiragem para a seringa ou cair para fora, permitindo que o fluxo de ar através do doseador para dispersar o pó. </li><li&gt; Feche a tampa do tubo de microcentrífuga. </li><li> Se não ser utilizada imediatamente, vedar a parte superior com uma pequena quantidade de laboratório-filme para minimizar a exposição do pó para a humidade ambiente. NOTA: De um modo geral, doseadores pré-carregadas devem ser armazenados de acordo com os requisitos de armazenamento do ingrediente farmactico activo (API). Muitas vezes, os pós de aerossol são sensíveis à humidade e deve ser armazenado dessecado. </li></ol> Atuação 4. Dispositivo <ol><li> Retire-se a seringa para o volume desejado, que pode ser específico para a aplicação. Para administração intrapulmonar em cobaias, utilizar 2 mL. Dispersão eficiência está relacionada com o volume e velocidade do ar emitido durante o accionamento, bem como as propriedades de dispersão inerentes do pó 7. O orifício superior do doseador acomoda uma seringa deslizamento-ponta. Uma seringa luer-lock pode ser utilizado com um adaptador. </li><li> Inserir a seringa na extremidade traseira do doseador. </li><li> Inserir a extremidade da agulha do doseador em tele dosagem porta na câmara de exposição. Deprimir a seringa com força, expelir o pó para fora do dispositivo e directamente no animal ou para dentro da câmara de exposição ou aparelho para análise (Figura 3). </li></ol>

<ol>
	<li>Young, E. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+Pyrazinoic+Acid+Esters+for+the+Treatment+of+Tuberculosis.">Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis.</a> Pharmaceutical Research. , 1-11 (2016).</li><li>Hinds, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles. , (2012).</li><li>Islam, N., Gladki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+inhalers+(DPIs)-A+review+of+device+reliability+and+innovation.">Dry powder inhalers (DPIs)-A review of device reliability and innovation.</a> International Journal of Pharmaceutics. 360 (1-2), 1-11 (2008).</li><li>Chan, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+aerosol+delivery+systems:+current+and+future+research+directions.">Dry powder aerosol delivery systems: current and future research directions.</a> J Aerosol Med. 19 (1), 21-27 (2006).</li><li>Vehring, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmaceutical+Particle+Engineering+via+Spray+Drying.">Pharmaceutical Particle Engineering via Spray Drying.</a> Pharmaceutical Research. 25 (5), 999-1022 (2008).</li><li>Bosquillon, C., Lombry, C., Pr&#233;at, V., Vanbever, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+formulation+excipients+and+physical+characteristics+of+inhalation+dry+powders+on+their+aerosolization+performance.">Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance.</a> Journal of Controlled Release. 70 (3), 329-339 (2001).</li><li>Hickey, A. J., Concessio, N. M., Van Oort, M. M., Platz, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+influencing+the+dispersion+of+dry+powders+as+aerosols.">Factors influencing the dispersion of dry powders as aerosols.</a> Pharmaceutical Technology. 18 (8), 58-64 (1994).</li><li>Garcia-Contreras, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+large+porous+particles+of+capreomycin+for+treatment+of+tuberculosis+in+a+guinea+pig+model.">Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.</a> Antimicrob Agents Chemother. 51 (8), 2830-2836 (2007).</li><li>Durham, P. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spray+Dried+Aerosol+Particles+of+Pyrazinoic+Acid+Salts+for+Tuberculosis+Therapy.">Spray Dried Aerosol Particles of Pyrazinoic Acid Salts for Tuberculosis Therapy.</a> Molecular Pharmaceutics. 12 (8), 2574-2581 (2015).</li><li>Sung, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+nitroimidazopyran+antibiotic+PA-824+aerosol+for+inhalation.">Dry powder nitroimidazopyran antibiotic PA-824 aerosol for inhalation.</a> Antimicrob Agents Chemother. 53 (4), 1338-1343 (2009).</li><li>Guillon, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+delivery+of+dry+powders+to+rats:+tolerability+limits+of+an+intra-tracheal+administration+model.">Pulmonary delivery of dry powders to rats: tolerability limits of an intra-tracheal administration model.</a> Int J Pharm. 434 (1-2), 481-487 (2012).</li><li>Morello, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry-powder+pulmonary+insufflation+in+the+mouse+for+application+to+vaccine+or+drug+studies.">Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies.</a> Tuberculosis. 89 (5), 371-377 (2009).</li></ol>

Portions of the pharmacokinetic data was presented at Respiratory Drug Delivery 2014 in Fajardo, Puerto Rico and dosator depictions and additional pharmacokinetic data were presented at the annual meeting of the American Association of Pharmaceutical Scientists 2015 in Orlando, Florida.

A dispersão dos doseadores era adequado para os animais para receber uma dose terapêutica por meio da respiração só de nariz passiva, indicando uma grande proporção de aerossol disperso ao tamanho de partículas primárias. Estes doseadores pode ser utilizada para a administração endotraqueal, avaliação in vitro do desempenho do pó, e para fins gerais de dispersão em aerossol de pó seco para experiências analíticas ou eficazes. Se for utilizado para entrega intrapulmonar, é importante o uso de ...

<html> Desenvolvimento de novos produtos terapêuticos exige testes de eficácia em um modelo animal. A via pulmonar de administração podem ser utilizados para entregar drogas localmente e sistemicamente um. Avaliação de aerossóis de pó seco requer um mecanismo de dispersão eficiente para manter concentrações elevadas numa câmara de exposição ou para administração directa endotraqueal. Enquanto existem soluções para expor os animais por inalação passiva de aerossóis de pó seco, a maioria requer massas de pó em grande excesso da dose administrada duas. Isto impede a realização de estudos de viabilidade iniciais como droga disponível é insuficiente para a pesquisa ou estágio inicial de desenvolvimento para suportar os requisitos de entrega de doses para sistemas de fornecimento de aerossol convencionais. Ao conceber um medicamento em aerossol, o desempenho aerodinâmico pode relacionar directamente com a eficiência de entrega e eficácia&gt; 3. Dispersão do pó num aerossol requer uma entrada de energia suficiente para vencer as forças de interparticulares, e abordagens de engenharia de partículas pode melhorar substancialmente o desempenho do aerossol 4, 5, 6. Nós desenvolvemos um sistema de dispersão (doseador), que pode atomizar aerossóis de pó seco Engineered eficiente para a finalidade de insuflação pulmonar directa, dispersão para um sistema de exposição ou geração para fins analíticos.

<table><tbody><tr><td>0.5 mL microcentrifuge tube</td><td>VWR</td><td>89000-026</td><td></td></tr><tr><td>High-Volume Particle-Filtering Stainless Steel Wire Cloth, Woven, 304 Stainless Steel, 60 x 60 Mesh, .0045&quot; Wire Diameter</td><td>McMaster Carr</td><td>9230T44</td><td></td></tr><tr><td>Stainless Steel Dispensing Needle, Straight, 18 Gauge, 1&quot; Long</td><td>McMaster Carr</td><td>75165A676</td><td>Any luer-fit needle will suffice</td></tr><tr><td>Cotton balls</td><td>McMaster Carr</td><td>54845T16</td><td></td></tr><tr><td>Parafilm M&amp;reg; Laboratory Film</td><td>VWR</td><td>100229-550</td><td></td></tr><tr><td>Black-Oxide High-Speed Steel Jobbers&#039; Drill Bit, Wire Gauge 22, 3-1/8&quot; Overall Length, 1.8&quot; Drill Depth, 135Deg Point</td><td>McMaster Carr</td><td>2901A195</td><td></td></tr></tbody></table>

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.

Para pós dispersáveis facilmente, tais como aqueles seco por pulverização com a intenção para entrega pulmonar 5, 8, 9, os doseadores entregar uma dose de bolus para fora do dispositivo. Existem muitas aplicações para os doseadores, incluindo a caracterização in vitro das partículas, a administração intrapulmonar directa em animais vivos, e a geração de aerossol para sist...

Watch this Scientific Journal Video about Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals at JoVE.com

Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

Durante o desenvolvimento de drogas para a administração pulmonar, é necessário avaliar a farmacocinética e eficácia num modelo animal. Apresenta-se um método para construir um sistema de dispersão de aerossol descartáveis ​​a partir de componentes de-the-shelf que podem ser usados ​​para administrar pó seco em aerossol intrapulmonar para roedores.

Doseadores descartável para Pulmonar insuflação de agentes terapêuticos para Pequenos Animais

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

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Research

JoVE Journal

Medicine

7.6K visualizações.  RTI International.  Durante o desenvolvimento de drogas para a administração pulmonar, é necessário avaliar a farmacocinética e eficácia num modelo animal. Apresenta-se um método para construir um sistema de dispersão de aerossol descartáveis ​​a partir de componentes de-the-shelf que podem ser usados ​​para administrar pó seco em aerossol intrapulmonar para roedores. 

Vídeo: Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

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.

Instilação traqueal direta de Solutos em pulmão de rato

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

Biologia

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.

Um método melhorado para rápida de intubação da traqueia em Ratos

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

Medicina

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.

Pó seco e nebulizada de inalação de aerossóis de produtos farmacêuticos entregue no Ratos Usando um nariz somente Sistema de Exposição

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.

Administração Intrabronquial direta para melhorar a deposição do agente seletivo dentro do pulmão do rato

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

Intratracheal Administration of Dry Powder Formulation in Mice

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper introduces a noninvasive method of intratracheal delivery of dry powder formulation in mice. A dry powder loading device that consists of a 200 &#181;L gel loading pipette tip connected to an 1 mL syringe via a three-way stopcock is presented. A small amount of dry powder (1-2 mg) is loaded into the pipette tip and dispersed by 0.6 mL of air in the syringe. Because pipette tips are disposable and inexpensive, different dry powder formulations can be loaded into different tips in advance. Various formulations can be evaluated in the same animal experiment without device cleaning and dose refilling, thereby saving time and eliminating the risk of cross-contamination from residual powder. The extent of powder dispersion can be inspected by the amount of powder remaining in the pipette tip. A protocol of intubation in mouse with a custom-made light source and a guiding cannula is included. Proper intubation is one of the key factors that influences the intratracheal delivery of dry powder formulation to the deep lung region of the mouse.

Dry powder formulations for inhalation have great potential in treating respiratory diseases. Before entering human studies, it is necessary to evaluate the efficacy of the dry powder formulation in preclinical studies. A simple and noninvasive method of the administration of dry powder in mice through the intratracheal route is presented.

Administração Intratraqueal de Formulação de Pó Seco em Camundongos

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

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications.
We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.

We describe a model of hydrochloric acid-induced acute respiratory distress syndrome (ARDS) in piglets receiving sedation with halogenated agents, isoflurane and sevoflurane, through a device used for inhaled intensive care sedation. This model can be used to investigate the biological mechanisms of halogenated agents on lung injury and repair.

Entrega de agente halogenado em modelo suíno de síndrome de angústia respiratória aguda através de um dispositivo tipo unidade de terapia intensiva

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent ...

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.

Um método minimamente invasivo para a instilação intratraqueal de drogas em roedores neonatais para tratar doenças pulmonares

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 ...

Dosadores descartáveis personalizáveis para administrar medicamentos em aerossol em pó seco a camundongos

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.

Autor em destaque: Desenvolvimento de um dosador descartável para testes pré-clínicos de inaladores de pó seco em modelos de pequenos animais 

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.

Dosadores descartáveis destinados à entrega de pó seco a ratos

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

Doseadores descartável para Pulmonar insuflação de agentes terapêuticos para Pequenos Animais

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Um método melhorado para rápida de intubação da traqueia em Ratos

Pó seco e nebulizada de inalação de aerossóis de produtos farmacêuticos entregue no Ratos Usando um nariz somente Sistema de Exposição

Administração Intrabronquial direta para melhorar a deposição do agente seletivo dentro do pulmão do rato

Administração Intratraqueal de Formulação de Pó Seco em Camundongos

Entrega de agente halogenado em modelo suíno de síndrome de angústia respiratória aguda através de um dispositivo tipo unidade de terapia intensiva

Um método minimamente invasivo para a instilação intratraqueal de drogas em roedores neonatais para tratar doenças pulmonares

Dosadores descartáveis destinados à entrega de pó seco a ratos

Dosadores descartáveis destinados à entrega de pó seco a ratos

Dosadores descartáveis destinados à entrega de pó seco a ratos