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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2001-9-26
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pubmed:abstractText |
To circumvent inherent problems associated with pulmonary administration of aqueous-solution and dry-powder protein drugs, inhalation delivery of proteins from their suspensions in absolute ethanol was explored both in vitro and in vivo. Protein suspensions in ethanol of up to 9% (wt/vol) were readily aerosolized with a commercial compressor nebulizer. Experiments with enzymic proteins revealed that nebulization caused no detectable loss of catalytic activity; furthermore, enzyme suspensions in anhydrous ethanol retained their full catalytic activity for at least 3 weeks at room temperature. With the use of Zn(2+)-insulin, conditions were elaborated that produced submicron protein particles in ethanol suspensions. The latter (insulin/EtOH) afforded respirable-size aerosol particles after nebulization. A 40-min exposure of laboratory rats to 10 mg/ml insulin/EtOH aerosols resulted in a 2-fold drop in the blood glucose level and a marked rise in the serum insulin level. The bioavailability based on estimated deposited lung dose of insulin delivered by inhalation of ethanol suspension aerosols was 33% (relative to an equivalent s.c. injection), i.e., comparable to those observed in rats after inhalation administration of dry powder and aqueous solutions of insulin. Inhalation of ethanol in a relevant amount/time frame resulted in no detectable acute toxic effects on rat lungs or airways, as reflected by the absence of statistically significant inflammatory or allergic responses, damage to the alveolar/capillary barrier, and lysed and/or damaged cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-10846014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-11196652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-11376972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-14076497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-1409359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-14213346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-14907713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-14934741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-3735078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-3892021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-494293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-6034420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-6169466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-6906368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-7333265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-7877966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-8031609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-8493526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-8956337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-9188534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-9487516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-9501969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11562495-9811498
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11103-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11562495-Administration, Inhalation,
pubmed-meshheading:11562495-Aerosols,
pubmed-meshheading:11562495-Animals,
pubmed-meshheading:11562495-Biological Availability,
pubmed-meshheading:11562495-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:11562495-Cattle,
pubmed-meshheading:11562495-Drug Stability,
pubmed-meshheading:11562495-Ethanol,
pubmed-meshheading:11562495-Glucuronidase,
pubmed-meshheading:11562495-Insulin,
pubmed-meshheading:11562495-L-Lactate Dehydrogenase,
pubmed-meshheading:11562495-Leukocytes,
pubmed-meshheading:11562495-Male,
pubmed-meshheading:11562495-Metabolic Clearance Rate,
pubmed-meshheading:11562495-Nebulizers and Vaporizers,
pubmed-meshheading:11562495-Proteins,
pubmed-meshheading:11562495-Rats,
pubmed-meshheading:11562495-Rats, Sprague-Dawley,
pubmed-meshheading:11562495-Zinc
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pubmed:year |
2001
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pubmed:articleTitle |
Inhalation delivery of proteins from ethanol suspensions.
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pubmed:affiliation |
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 01239, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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