Autori desiderano ringraziare gentilmente l&#39;Istituto Nazionale per le allergie e le malattie infettive per il finanziamento per lo svolgimento di questa ricerca.

1. Preparazione di componenti della Dosators <ol><li> Perforare la parte inferiore di una provetta 0,5 mL polipropilene perforando o semplicemente molatura o tagliare il fondo con una mola o un paio di forbici. Assicurarsi che il foro nel centro e non è superiore a 2 mm di diametro e non meno di 1 mm di diametro (Figura 1). </li><li> Perforare la parte superiore della provetta. Utilizzando un # 22 punta di trapano (circa 4 mm di diametro), praticare un foro al centro del tappo. Ciò si traduce in un foro che si adatta una siringa slip-tip (Figura 1). </li><li> Preparare fini schermate da inserire nelle provette da microcentrifuga. Rendere schermi da 304 tela metallica in acciaio inox, 60 x 60 mesh con diametro del filo di 0,0045&quot; . Tagliare le schermate con cesoie o punzone utilizzando uno stampo ad un diametro esterno di 5 mm (figura 2). </li></ol> 2. Assemblea della Dosators <ol><li> Utilizzando sia pinze o l&#39;estremità di un ago punta smussata, inserire lo schermo nella provetta e alloggiarlo in basso in modo che esso copre l&#39;apertura. Questo servirà a sostenere la polvere prima dell&#39;attivazione. </li><li> Press Fit l&#39;estremità più stretta della punta microcentrifuga nell&#39;estremità di un ago punta smussata. A tale scopo, a mano o con una pressa da banco e una guida. Pulire delicatamente la parte superiore dell&#39;ago e inferiore del tubo con etanolo per pulire le parti per garantire una stretta, vestibilità resiliente. </li></ol> 3. Riempire il Dosators <ol><li> Utilizzando una microbilancia analitica, tarare il dispositivo e caricare la quantità desiderata di polvere nel dosatore. Un tipico massa di polveri per la dispersione varia da 1 a 10 mg. </li><li> Una volta riempito, collegare la parte superiore della provetta con un&#39;assegnazione di cotone e un paio di pinze. Ciò impedirà la polvere dal disegno nella siringa o caduta, pur consentendo il flusso d&#39;aria attraverso il dosatore per disperdere la polvere. </li><li&gt; chiudere il tappo provetta. </li><li> Se non viene utilizzato immediatamente, sigillare la parte superiore con una piccola quantità di laboratorio pellicola per minimizzare l&#39;esposizione polvere all&#39;umidità ambientale. NOTA: Generalmente, dosators precaricati devono essere conservati in base alle esigenze dell&#39;ingrediente farmaceutico attivo (API) di stoccaggio. Spesso polveri aerosol sono sensibili all&#39;umidità e devono essere conservati essiccato. </li></ol> 4. Dispositivo di azionamento <ol><li> Arretrare la siringa al volume desiderato, che può essere specifica applicazione. Per la somministrazione intrapolmonare in cavie, utilizzare 2 ml. Efficienza dispersione è correlata al volume e la velocità dell&#39;aria erogata durante l&#39;azionamento, come pure le proprietà di dispersione intrinseche della polvere 7. Il foro superiore del dosatore ospita una siringa slip-punta. Una siringa Luer-lock può essere utilizzato con un adattatore. </li><li> Inserire la siringa nel back-end del dosatore. </li><li> Inserire l&#39;estremità ago del dosatore in tegli dosaggio porta sulla camera di esposizione. Deprimere la siringa con forza, espellendo polvere dal dispositivo e direttamente nell&#39;animale o nella camera di esposizione o strumento analitico (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.

La dispersione dei dosators era adatto per animali ricevono una dose terapeutica mediante la respirazione naso sola passivo, indicando una grande proporzione di aerosol dispersi per dimensioni delle particelle primarie. Questi dosators possono essere usate per la somministrazione endotracheale, nella valutazione delle prestazioni vitro polvere, e scopo generale polvere secca dispersione aerosol per esperimenti analitici o efficaci. Se utilizzato per la consegna intrapolmonare, è importante utilizzare ...

<html> Sviluppo di nuovi prodotti terapeutici richiede prove di efficacia in un modello animale. La via di somministrazione polmonare può essere utilizzato per fornire farmaci a livello locale e sistemica 1. Valutazione di aerosol in polvere secca richiede un meccanismo efficiente dispersione di mantenere elevate concentrazioni in camera di esposizione o per somministrazione diretta endotracheale. Mentre le soluzioni esistono per esporre gli animali per inalazione passiva ad asciugare aerosol in polvere, la maggior parte richiedono masse di polvere in grande eccesso della dose erogata 2. Questo preclude la realizzazione di studi di fattibilità già nel farmaco insufficiente è disponibile presso la ricerca o fase iniziale di sviluppo per sostenere le esigenze di consegna della dose per i sistemi di erogazione di aerosol convenzionali. Durante la progettazione di un prodotto di droga aerosol, le prestazioni aerodinamiche può riguardare direttamente l&#39;efficienza e l&#39;efficacia di consegna&gt; 3. Dispersione di polvere in un aerosol richiede l&#39;input di energia sufficiente a superare le forze interparticulate, e le soluzioni tecniche particella può migliorare sostanzialmente le prestazioni aerosol 4, 5, 6. Abbiamo sviluppato un sistema di dispersione (dosatore) che può aerosolizzare ingegneristiche aerosol di polvere secca efficiente ai fini di insufflazione polmonare diretta, dispersione in un sistema di esposizione o di generazione per scopi analitici.

<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.

Per le polveri dispersibili facilmente come quelli essiccato a spruzzo con l&#39;intento di consegna polmonare 5, 8, 9, i dosators consegnare un bolo dal dispositivo. Ci sono molte applicazioni per le dosators, incluse caratterizzazione in vitro delle particelle, amministrazione intrapolmonare diretto di animali vivi, e la generazione di aerosol per inalazione sistemi passivi. <p cl...

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 lo sviluppo di farmaci per la consegna polmonare, è necessario valutare la farmacocinetica e l&#39;efficacia in un modello animale. Presentiamo un metodo per costruire un sistema aerosol dispersione monouso da componenti of-the-shelf che possono essere utilizzati per somministrare intrapolmonari aerosol polvere secca per roditori.

Monouso Dosators per insufflazione polmonare di agenti terapeutici ai piccoli animali

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

disposable-dosators-for-pulmonary-insufflation-therapeutic-agents-to

Research

JoVE Journal

Medicine

7.6K Views.  RTI International.  Durante lo sviluppo di farmaci per la consegna polmonare, è necessario valutare la farmacocinetica e l'efficacia in un modello animale. Presentiamo un metodo per costruire un sistema aerosol dispersione monouso da componenti of-the-shelf che possono essere utilizzati per somministrare intrapolmonari aerosol polvere secca per roditori. 

Video: 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.

Diretta instillazione tracheale di soluti in polmone mouse

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

Ricerca

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.

Un metodo migliore per Rapid intubazione della trachea nei topi

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.

Polvere secca e nebulizzata Aerosol L&#39;inalazione di prodotti farmaceutici distribuito nelle topo, utilizzando un naso-only Sistema di esposizione

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.

Amministrazione intrabronchiale diretta per migliorare la deposizione selettiva dell'agente all'interno del polmone del mouse

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.

Somministrazione intratracheale della formulazione di polvere secca nei topi

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.

Somministrazione di agenti alogenati in modelli suini di sindrome da distress respiratorio acuto tramite un dispositivo di tipo unità di 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.

Un metodo minimamente invasivo per l'instillazione intratracheale di farmaci nei roditori neonatali per il trattamento delle malattie polmonari

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 ...

Dosatori monouso personalizzabili per erogare farmaci aerosol in polvere secca ai topi

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.

Autore in primo piano: Sviluppo di un dosatore monouso per test preclinici di inalatori di polvere secca in piccoli modelli animali 

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.

Dosatori monouso destinati alla somministrazione di polvere secca ai topi

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

Monouso Dosators per insufflazione polmonare di agenti terapeutici ai piccoli animali

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Capitoli in questo video

Diretta instillazione tracheale di soluti in polmone mouse

Un metodo migliore per Rapid intubazione della trachea nei topi

Polvere secca e nebulizzata Aerosol L'inalazione di prodotti farmaceutici distribuito nelle topo, utilizzando un naso-only Sistema di esposizione

Amministrazione intrabronchiale diretta per migliorare la deposizione selettiva dell'agente all'interno del polmone del mouse

Somministrazione intratracheale della formulazione di polvere secca nei topi

Somministrazione di agenti alogenati in modelli suini di sindrome da distress respiratorio acuto tramite un dispositivo di tipo unità di terapia intensiva

Un metodo minimamente invasivo per l'instillazione intratracheale di farmaci nei roditori neonatali per il trattamento delle malattie polmonari

Dosatori monouso destinati alla somministrazione di polvere secca ai topi

Dosatori monouso destinati alla somministrazione di polvere secca ai topi

Dosatori monouso destinati alla somministrazione di polvere secca ai topi