저자에 친절하게 좋아하는이 연구를 수행 할 수있는 자금에 대한 알레르기 및 전염병 국립 연구소 감사합니다.

Dosators의 부품의 제조 1 <ol><li> 뚫어하거나 또는 연삭 숫돌이나 위의 날카로운 한 쌍의 하단을 절단하여 0.5 ㎖의 폴리 프로필렌 미세 원심 튜브의 바닥을 관통. 구멍이 중앙에 직경하게는 2 mm 이상의 직경보다 작지 1 mm (도 1)인지 확인. </li><li> microcentrifuge 관의 상단을 관통. A # 22 드릴 비트 (직경이 약 4mm)를 사용하여 캡의 중앙에 구멍을 드릴. 이것은 슬립 주사기 팁 (도 1)에 맞는 구멍을 초래한다. </li><li> 준비 미세한 스크린은 마이크로 원심 튜브에 삽입한다. . 304 스테인리스 철망 &quot;0.0045 선 직경 60 X 60 메쉬의 스크린을 주석 자르는으로 화면 컷 또는 5mm (도 2)의 외경에 다이를 사용하여, 펀치. </li></ol> Dosators 2. 총회 <ol><li> 어느 겸자 무딘 팁 바늘의 끝을 사용하여, 마이크로 원심 튜브에 화면을 삽입하고 개구부를 덮도록 바닥에 안착. 이 작동하기 전에 분말을 지원하는 역할을합니다. </li><li> 눌러 뭉툭한 팁 바늘의 끝 부분에 마이크로 원심 끝의 좁은 끝을 맞습니다. 손으로 또는 벤치 탑 프레스 및 가이드와 함께이 작업을 수행합니다. 부드럽게 꽉 탄력 적합을 보장하기 위해 부품을 청소하는 에탄올로 튜브의 바늘과 하단의 상단을 닦으십시오. </li></ol> 3. Dosators를 작성 <ol><li> 분석 마이크로 저울을 사용하여 용기를 장치하고 dosator 분말에 소 정량의로드. 분산의 일반적인 분말 덩어리는 1 내지 10 mg의 범위이다. </li><li> 일단 채워진면의 분담 및 한 쌍의 집게로 microcentrifuge 관의 상단 플러그. 이 주사기에 그리거나 분말을 분산하기 위해 dosator로 공기 흐름을 허용하면서, 밖으로 떨어지는 분말을 방지 할 수 있습니다. </li><l난&gt;은 microcentrifuge 관 뚜껑을 닫습니다. </li><li> 즉시 사용하지 않는 경우, 주변 습도에 분말의 노출을 최소화하도록 랩 필름 소량의 상단을 밀봉. 주 : 일반적으로, 프리로드 dosators 활성 제약 성분 (API)의 저장 요구에 따라 저장한다. 종종 에어로졸 분말은 민감한 습기하고 건조 된 보관해야합니다. </li></ol> 4. 장치 작동 <ol><li> 응용 프로그램의 특정 될 수있다 원하는 볼륨에 주사기를 다시 그립니다. 기니 돼지 폐내 투여를 위해,이 용액을 사용한다. 분산 효율은 볼륨 및 작동시 전달되는 공기의 속도뿐만 아니라, 분체 (7)의 고유 산성 관련된다. dosator의 상단 구멍 슬립 팁 주사기를 수용한다. 루어 락 주사기는 어댑터와 함께 사용할 수있다. </li><li> dosator의 백 엔드에 주사기를 삽입합니다. </li><li> t에 dosator의 바늘 끝을 삽입그는 노출 챔버에 포트를 투여. 장치로부터 직접 또는 동물에 노출 챔버 또는 분석 기기 (도 3)로 분말을 추방 강제 주사기 우울. </li></ol>

<ol>
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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.

동물 차 입자 크기로 분산 된 에어로졸의 큰 비율을 나타내는 수동적 코 호흡만을 통해 치료 용량을 수신위한 dosators로부터 분산액이 적합했다. 이러한 분석은 dosators 또는 효능 실험 관내 분말 성능 평가, 다목적 건조 분말 에어로졸 분산, 기관 내 투여 용으로 사용될 수있다. 폐내 전달을 위해 사용되는 경우, 조직 손상의 원인 및 약동학 적 결과를 왜곡 할 수 이상 - 인플레이션 폐의로, 선택한 종족에 대한 공기의 적절한 볼륨을 사용하는 것이 중요합니다. 5 ㎖의 체적은 다소 다른 연구는 폐 손상은 단일 2 mL의 투여 11 래트에서 발생할 수 있음을 보여 주었다 유사한 장치 (10)와 기니아 피그에서 사용되어왔다. 때문에 구성 요소 및 준비의 용이성의 비용으로, 이러한 dosators은 단일 사용 일회용으로 사용할 수 있습니다.대조적으로, 다목적 장치는 장치를 투여하는 단계 (12)를 다시 채워야하는 사이에, 동물 실험의 성능을 복잡하고 대부분의 시설에서 쉽게 달성되지 않는 작업을 수행하는 동물의 기술자를 필요로하는 것이 필요하다. 필링은 (투여 챔버 내로 계량 작은 질량을 지원하기 위해 저울 후드 또는 글러브 박스와 공급로) 투여 제제 실험실에서 수행 될 수 있으며, 샘플은 동물 절차 방 오히려 동일한 실험실에서 수행 모두 활성을 갖는로 전송 될 수있다. 추가 생물학적 방제 임의의 형태가 동물 실험을 위해 필요한 경우에 특히 유리하다. 우리는 여기서 용이하게 제조 할 수 있으며, 효율적으로 최소한의 약물 사용과 초기 단계 에어로졸 약물 개발을 촉진 할 수있는 분산 시스템의 제조에 적합한 방법을 보여줍니다. 저가 dosators는 대량 제조 및 투여 프리로드 (F)로서 사용될 수있다필요한 개인 보호 장비가 방해 될 수 제한 환경에서 에어로졸 분말을 관리 ORMS (도 7).

<html> 새로운 치료제의 개발은 동물 모델에서 효능 테스트를 필요로한다. 폐 투여 경로는 국소 적 및 전신적 1 약물을 전달하기 위해 이용 될 수있다. 건조 분말 에어로졸 평가 노광 챔버에 직접 또는 기관 내 투여 용으로 높은 농도를 유지하는 효율적인 분산 메커니즘을 필요로한다. 솔루션은 분말 에어로졸을 건조 수동 흡입에 의해 동물을 노출 존재하지만, 대부분은 2 전달 용량의 과량으로 분말의 질량을 필요로한다. 이 연구 또는 초기 개발 단계는 기존의 에어로졸 전달 시스템의 용량 전송 요구 사항을 지원하기에 불충분 한 약물을 사용할 수 조기 타당성 조사를 실시 배제. 에어로졸 제제를 설계 할 때, 공기 역학적 성능을 전달 효율과 효능에 직접 관련 될 수&gt; 3. 에어로졸 분말로 분산 interparticulate 힘을 극복하기에 충분한 에너지 입력을 필요로하고, 입자 공학적 접근 실질적 에어로졸 성능 4, 5, 6을 향상시킬 수있다. 우리의 분석을 위해 노광 시스템이나 폐 생성에 직접 취입, 분산 목적으로 효율적으로 설계된 건조 분말 에어로졸을 에어로졸 화 할 수있는 분산 시스템 (dosator)를 개발 하였다.

<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.

같은 쉽게 산성 분말 용 분무 건조 된 폐 전달 5, 8, 9 의도에서, dosators 장치로부터 일시 투여 전달 이들. 수동 흡입 시스템을위한 생체 입자 특성, 살아있는 동물에서 직접 폐내 관리 및 에어로졸 세대를 포함하여 dosators에 대한 많은 응용 프로그램이 있습니다. dosators 분말이 분산액의 효율을 증명하기 위해, 이전에 구성된 코 만 노출 챔버를 이용 하였다. 이 챔버의 주요 특징은 높은 에어로졸 농도가 달성 될 수 있도록 작은 중앙 챔버 낮은 기류이다. 도징 챔버 아크릴 조립 및 &quot;직경 및 3의 길이&quot;중앙 에어로졸 구획실 4 테이퍼 노즈 콘 추천 된패시브 흡입 (도 4)에 의해 에어로졸 노출 평가. 공기 역학적 평균 직경 (MMAD) 2.9 ㎛의 분무 건조 된 분말 약물이 시스템 (도 5)를 이용하여 기니아 피그에서 평가 하였다. 투여 간격은 12 mL를 주사기를 사용하여 5 mg의 단일 일시 투여 전달 후 실시간 챔버 농도를 측정함으로써 결정 하였다. 로 3 분 간격으로 10 mg의 5 투여 량을 투여 생체 내 평가에서 5 ㎍ / ㎖ (도 6)의 최대 혈중 농도 결과. 이것은 널리 필드 (10)에 사용하는 시스템이 제공 1 ㎎ / ㎏의 투여 량 endotracheally 비교. 패시브 흡입의 결과로서 관찰 혈장 농도가 일차 입자 크기를 효율적으로 분산을 나타낸다. 참족 내부없이 공기 흐름이 거의 존재하므로<html> BER, 에어로졸 농도는 입자가 중력 침강에 의한 탈락과 같은 입자의 공기 역학적 직경의 함수로서 감소한다. 입자의 침전 및 에어로졸의 농도가 소정 임계 값 이하로 감소함에 따라, 다른 투여 량은 포트를 통해 투여 될 수있다. 노출 시간은 목적에 달려 있지만, 고농도가 달성되기 때문에, 일정 시간의 노출을 최소화하기 위해 결정될 수있다. 이것은 다시 이러한 일회용 투약 시스템을 사용하는 하나의 응용 프로그램을 설명하지만, 또 다른 가능한 사용은 평가의 목적에 따라 많은 분석 엔드 포인트를 가질 수 있습니다 직접 폐내 분말 관리 될 것입니다. <img alt="그림 1" src="/files/ftp_upload/55356/55356fig1.jpg" /> 도 1은 원심 분리 튜브를 수정. 하부 및 상부에 구멍을 0.5 ㎖의 마이크로 원심 튜브를 수정.<html> .JPG &quot;target =&quot;_ blank &quot;&gt; 검색이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오. <img alt="그림 2" src="/files/ftp_upload/55356/55356fig2.jpg" /> 그림 2. 메쉬 화면. 와이어 직경 0.0045 &quot;60 X 60 스테인레스 스틸 메쉬의 5mm 직경의 원. <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55356/55356fig2large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 3" src="/files/ftp_upload/55356/55356fig3.jpg" /> 3. 발동 도식 그림. 분말의 개략적 묘사 구동 dosator 조립. 공기 분배 끝에서 분말을 분산, 저수지 통해 강제된다. <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55356/55356fig3large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <html> 1 &quot;&gt; :&quot;유지 - together.within 페이지 = FO &quot;e_content <img alt="그림 4" src="/files/ftp_upload/55356/55356fig4.jpg" /> 4. 노출 상공 회의소 회로도를 그림. 치수 동물 노출 챔버 중앙 저장 개략도. 각 동물은 테이퍼 노즈 콘을 통해 상기 중앙 챔버로 유도되는 두 동물을 한번에 노광 할 수있다. <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55356/55356fig4large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 5" src="/files/ftp_upload/55356/55356fig5.jpg" /> 5. 건조 분말 에어로졸 그림. 분무 건조에 의해 제조 된 대표적인 약물 설계 분말. 분말은 다양한 애플리케이션을 위해 설계 될 수있다. 설계 건조 분말 에어로졸 공기 역학적 직경 분말 분산 효율이 중요한 설계 목표이다. 스케일 바는 = 5 개 미크론.COM / 파일 / ftp_upload / 55356 / 55356fig5large.jpg &quot;target =&quot;_ blank &quot;&gt; 검색이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오. <img alt="그림 6" src="/files/ftp_upload/55356/55356fig6.jpg" /> 도 6 수동 흡입 통한 약동학 평가. 1 밀리그램의 기준 용량에 비해 중앙 에어로졸 저장조에 dosators 의해 분산을 5 시간에 걸쳐 로그 스케일에서 약물의 플라즈마 농도의 약물 동력학 / 폐에 직접 투여에 의해 전달 kg이다. <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55356/55356fig6large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> <img alt="그림 7" src="/files/ftp_upload/55356/55356fig7.jpg" /> 그림 7. 채워진 및 대량 Dosators. (좌) 및 충진 구동 준비 dosator (10 mg)을 얻었다. (권리) </strong&gt; 일회용 dosators 대량 제조 묘사. 이러한 제한된 환경에서 사용하기 위해 미리로드 할 수 있습니다. <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55356/55356fig7large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a>

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

폐 전달을위한 약물의 개발 과정은 동물 모델에서 약물 동력학과 효능을 평가하는 것이 필요하다. 우리는 설치류 폐내 건조 분말 에어로졸을 투여하는데 사용될 수의 상용 성분으로부터 일회용 에어로졸 분산 시스템을 구축하는 방법을 제시한다.

작은 동물에 대한 치료제의 폐 통기를위한 일회용 Dosators

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

Nanyang Technological University

Research

JoVE Journal

Medicine

7.6K 조회수.  RTI International.  폐 전달을위한 약물의 개발 과정은 동물 모델에서 약물 동력학과 효능을 평가하는 것이 필요하다. 우리는 설치류 폐내 건조 분말 에어로졸을 투여하는데 사용될 수의 상용 성분으로부터 일회용 에어로졸 분산 시스템을 구축하는 방법을 제시한다. 

비디오: 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.

마우스 폐에 Solutes 직접 Tracheal 떨어뜨림

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

연구

생물학

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.

마우스의기도 신속 삽관 용 개선 된 방법

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

의학

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.

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.

마우스 폐 내 선택적 에이전트 침착을 개선하기 위한 직접 기관내 투여

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.

쥐에서 건조 분말 제형의 장내 투여

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.

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.

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 ...

건조 분말 에어로졸 약물을 마우스에 전달하기 위한 맞춤형 일회용 투여기

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.

저자 스포트라이트: 소동물 모델에서 건조 분말 흡입기의 전임상 테스트를 위한 일회용 투여제 개발 

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.

생쥐에 건조 분말을 전달하기 위한 일회용 투여제

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

작은 동물에 대한 치료제의 폐 통기를위한 일회용 Dosators

요약

더 많은 비디오 탐색

이 비디오의 챕터

마우스 폐에 Solutes 직접 Tracheal 떨어뜨림

마우스의기도 신속 삽관 용 개선 된 방법

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

마우스 폐 내 선택적 에이전트 침착을 개선하기 위한 직접 기관내 투여

쥐에서 건조 분말 제형의 장내 투여

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

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

생쥐에 건조 분말을 전달하기 위한 일회용 투여제

생쥐에 건조 분말을 전달하기 위한 일회용 투여제

생쥐에 건조 분말을 전달하기 위한 일회용 투여제