Co-spray dried resveratrol and budesonide microparticles: Preparation, characterization and anti-inflammatory activity on alveolar macrophages

Valentina Trotta, Wing-Hin Lee, Ching-Yee Loo , Santo Scalia, Paul M. Young, Daniela Traini

Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Patients with severe COPD are sometime afflicted by corticosteroid’ unresponsiveness due to inhibited histone deacetylase (HADC2) activity in alveolar macrophages. Therefore, novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroids responses in COPD patients. In this study, an inhalable microparticle formulation containing resveratrol (RES) and budesonide (BD) was developed.
The co-spray dried (co-SD) RES and BD microparticles were produced using a Buchi B-290 Spray dryer and their morphologies and aerosol performances characterized using scanning electron microscopy (SEM) and multi stage liquid impinger (MSLI), respectively. The effect of spray-dried RES and BD, alone and in combination, on cell viability were investigated against a NR8383 alveolar macrophages cell line. The extent of anti-inflammatory activity of RES and BD, alone and in combination was also studied on lipopolysaccharides (LPS) induced NR8383 cells.
The co-SD microparticles of all formulations exhibited morphologies appropriate for inhalation administration, as observed by SEM. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in LPS induced alveolar macrophages.
Single, co-SD RES and BD microparticles exhibited morphology and aerosol properties suitable for inhalation drug delivery. In vitro studies showed that alveolar macrophages could tolerate concentrations of RES and BD from 1.25 to 80μM and both were able to reduce the levels of TNF-α and IL-6 in a time dependent manner.

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