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Droplet aerodynamics, cellular uptake and efficacy of a nebulizable corticosteroid nanosuspension are superior to a micronized dosage form

Britland, Stephen, Finter, Wayne, Chrystyn, Henry, Eagland, Donald and Abdelrahim, Mohamed E. (2012) Droplet aerodynamics, cellular uptake and efficacy of a nebulizable corticosteroid nanosuspension are superior to a micronized dosage form. Biotechnology Progress, 28 (5). pp. 1152-1159. ISSN 8756-7938

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Abstract

Inhaled corticosteroids are considered to be an effective prophylactic against the morbid symptoms of several lung diseases, but scope remains for improvement in drug delivery technology to benefit bioavailability and treatment compliance. To ascertain whether dosage form might influence bioavailability, the emission characteristics and efficacy of a nanoparticulate budesonide formulation (Nanagel®) were compared with those of a proprietary micronized suspension (Pulmicort®) when delivered as a nebulized aerosol to human airway epithelial cells in a culture model. Having the visual appearance of a clear solution, Nanagel® was delivered by both jet and vibrating mesh nubulizers as an increased fine particle fraction and with a smaller mass median aerodynamic diameter (MMAD) compared to the micronized suspension. Quantitative high performance liquid chromatography (HPLC) analysis of cultured epithelia one hour after treatment with Nanagel®revealed a significantly greater cellular accumulation of budesonide when compared with Pulmicort® for an equivalent dose, a differential which persisted 24 and 48 hours later. A quantitative in vitro assay measuring the activity of enzymes involved in superoxide production revealed that stressed HaCaT cells (a long-lived, spontaneously immortalized human keratinocyte line) treated with Nanagel®continued to show significantly greater attenuation of inflammatory response compared with Pulmicort®-treated cells 24-hours after the application of an equivalent budesonide dose. The present in vitro findings suggest that formulation of inhalable drugs such as budesonide as aerosolized nanoparticulate, rather than microparticulate, suspensions can enhance bioavailability with concomitant improvements in efficacy

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Sharon Beastall
Date Deposited: 11 Sep 2012 09:55
Last Modified: 07 Feb 2013 09:42
URI: http://eprints.hud.ac.uk/id/eprint/14783

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