NDLI: Inhalation delivery of proteins from ethanol suspensions.

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Inhalation delivery of proteins from ethanol suspensions.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Langer, R. Klibanov, A. M. Choi, W. S. Edwards, D. A. Murthy, G. G.
Description	Author Affiliation: Choi WS ( Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 01239, USA.);
Abstract	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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bronchoalveolar Lavage Fluid Chemistry Insulin Administration & Dosage Pharmacokinetics Proteins Administration, Inhalation Aerosols Animals Biological Availability Cytology Drug Stability Ethanol Toxicity Glucuronidase Blood L-Lactate Dehydrogenase Leukocytes Metabolic Clearance Rate Nebulizers And Vaporizers Rats, Sprague-Dawley Zinc Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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