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
nebulizers 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 h 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 h 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.