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

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.

Recombinant Lucilia sericata chymotrypsin in a topical hydrogel formulation degrades human wound eschar ex vivo.

Larval biotherapy is a debridement tool used in wound management. The mechanism of action involves degradation of eschar by serine proteases including chymotrypsin within the alimentary fluids of first instar Lucilia sericata. With the rationale of obviating some limitations of biotherapy, including cost, complexity of use, and patient reticence, the present study describes a mobile hydrogel formulation containing freeze-dried recombinant L. sericata chymotrypsin designed for topical application. Neither freeze-drying nor formulation into the hydrogel significantly attenuated the measured activity of released enzyme compared to fresh-frozen enzyme in aqueous solution. Gel electrophoresis confirmed qualitatively that the chymotrypsin/hydrogel formulation both with and without supplementary urea at 10% (w) /(v) degraded human chronic wound eschar ex vivo. Mindful that the hallmark of intractability of chronic wounds is aberrant biochemistry, the pH activity profile for the enzyme/hydrogel formulation was compared with exudate pH in chronic wounds of mixed aetiology in a cohort of 48 hospital in-patients. Five patients' wounds were acidic, however, the remainder were predominantly alkaline and coincided with the pH optimum for the insect enzyme. Thus, a recombinant L. sericata chymotrypsin and hydrogel formulation could represent a pragmatic alternative to larval therapy for the management of chronic wounds.