title: Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages.
abstract: Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroid responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratios of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90 l/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. 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 tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages. This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced efficacy to control inflammation and oxidative stress in LPS-induced alveolar macrophages.
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Trotta
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Wing-Hin
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Ching-Yee
authors.initials: CY
authors.lastname: Loo
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia. Electronic address: daniela.traini@sydney.edu.au.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Scalia
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D019819:Budesonide / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003890:Desiccation; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology; D013678:Technology, Pharmaceutical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000336:Aerosols; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D019819:Budesonide; D000077185:Resveratrol
keywords: Alveolar macrophage; Anti-inflammatory; Anti-oxidant; Budesonide; Chronic obstructive pulmonary disease; Dry powder inhalation; Resveratrol