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

Forfattere vil gerne venligt takke det nationale institut for Allergi og Smitsomme Sygdomme for midler til at udføre denne forskning.

1. Fremstilling af Komponenter af dosatorerne <ol><li> Perforere bunden af ​​en 0,5 ml polypropylen mikrocentrifugerør ved boring eller ved simpelthen at slibe eller afskære bunden med en slibeskive eller en skarp saks. Sikre, at hullet er i centrum og er ikke mere end 2 mm i diameter og ikke mindre end 1 mm i diameter (figur 1). </li><li> Perforere toppen af ​​mikrocentrifugerør. Anvendelse af en # 22 borehoved (ca. 4 mm i diameter), bore et hul i midten af ​​hætten. Dette resulterer ...

<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>

Dispersionen fra dosatorerne var egnet til dyr for at modtage en terapeutisk dosis via passiv kun næsen respiration, hvilket indikerer en stor del af aerosol spredt til primær partikelstørrelse. Disse dosatorerne kan anvendes til endotracheal administration, in vitro-vurdering af pulver ydeevne og generelle formål tørpulveraerosol dispersion til analytiske eller virkningsfulde eksperimenter. Hvis de anvendes til intrapulmonær levering, er det vigtigt at anvende et passende volumen af ​​luft til de val...

<html> Udvikling af nye lægemiddelprodukter kræver effektivitetsforsoegene i en dyremodel. Den pulmonale administrationsvej kan anvendes til at tilføre lægemidler lokalt og systemisk 1. Evaluering af Tørpulveraerosoler nødvendiggør en effektiv dispersion mekanisme til at opretholde høje koncentrationer i et eksponeringskammer eller til direkte endotracheal administration. Mens der findes løsninger til at eksponere dyrene ved passiv inhalering til Tørpulveraerosoler, de fleste kræver masser af pulver i stort overskud af den afgivne dosis 2. Dette udelukker ledende tidlige forundersøgelser som utilstrækkelig lægemiddel er tilgængelig på forskning eller tidlig fase for at fremme kravene dosis leveringsbetingelser for konventionelle aerosol administrationssystemer. Ved udformningen af ​​en aerosol lægemiddelprodukt, kan aerodynamisk ydeevne vedrører direkte levering effektivitet og effekt&gt; 3. Dispersion af pulver til en aerosol kræver energitilførsel tilstrækkelig til at overvinde interpartikulære kræfter, og partikel tekniske tiltag, kan det forbedre aerosolydelse 4, 5, 6. Vi har udviklet et dispersionssystem (doseringsapparat), som kan aerosolisere gensplejsede Tørpulveraerosoler effektivt med henblik på direkte pulmonal insufflation dispersionen i en eksponering system eller generation til analytiske formål.

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			<td height="21" style="height:21px;width:695px;">0.5 mL microcentrifuge tube</td>
			<td style="width:139px;">VWR</td>
			<td style="width:119px;">89000-026</td>
			<td style="width:207px;"></td>
		</tr>
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			<td height="23" style="height:23px;">High-Volume Particle-Filtering Stainless Steel Wire Cloth, Woven, 304 Stainless Steel, 60 x 60 Mesh, .0045&#34; Wire Diameter</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">9230T44</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stainless Steel Dispensing Needle, Straight, 18 Gauge, 1&#34; Long</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">75165A676</td>
			<td>Any luer-fit needle will suffice</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:695px;">Cotton balls</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">54845T16</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:695px;">Parafilm M&#174; Laboratory Film</td>
			<td style="width:139px;">VWR</td>
			<td>100229-550</td>
			<td></td>
		</tr>
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			<td height="21" style="height:21px;">Black-Oxide High-Speed Steel Jobbers&#39; Drill Bit, Wire Gauge 22, 3-1/8&#34; Overall Length, 1.8&#34; Drill Depth, 135Deg Point</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">2901A195</td>
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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.

For let dispergerbare pulvere, såsom dem spraytørret med den hensigt til pulmonal levering 5, 8, 9, de dosatorerne levere en bolusdosis ud af indretningen. Der er mange anvendelser for dosatorerne, herunder in vitro-partikel karakterisering, direkte intrapulmonær indgivelse i levende dyr, og aerosoldannelse for passive inhalationssystemer. <p class="jove_content" fo:keep-together...

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

Under udviklingen af ​​lægemidler til pulmonal levering, er det nødvendigt at vurdere farmakokinetik og effekt i en dyremodel. Vi præsenterer en fremgangsmåde til at bygge en engangs aerosol dispersionssystem fra of-the-shelf komponenter, der kan anvendes til indgivelse af intrapulmonal tørpulveraerosol til gnavere.

Engangs dosatorerne til pulmonal Insufflation af terapeutiske midler til smådyr

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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