In vitro biological activity of resveratrol using a novel inhalable resveratrol spray-dried formulation

Int J Pharm. 2015 Aug 1;491(1-2):190-7. doi: 10.1016/j.ijpharm.2015.06.033. Epub 2015 Jun 24.

Abstract

The aim of the study was to prepare inhalable resveratrol by spray drying for the treatment of chronic obstructive pulmonary disease (COPD). Resveratrol, with a spherical morphology and particle diameter less than 5 μm, was successfully manufactured. Fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of spray-dried resveratrol was 39.9 ± 1.1% and 3.7 ± 0.1 μm, respectively, when assessed with an Andersen cascade impactor (ACI) at 60 l/min. The cytotoxicity results of resveratrol on Calu-3 revealed that the cells could tolerate high concentration of resveratrol (up to 160 μM). In addition, in transport experiments using Snapwells, it was observed that more than 80% of the deposited dry powder was transported across the Calu-3 cells to the basal chamber within four hours. The expression of interleukin-8 (IL-8) from Calu-3 induced with tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β1) and lipopolysaccharide (LPS) were significantly reduced after treatment with spray-dried resveratrol. The antioxidant assay (radical scavenging activity and nitric oxide production) showed spray-dried resveratrol to possess an equivalent antioxidant property as compared to vitamin C. Results presented in this investigation suggested that resveratrol could potentially be developed as a dry powder for inhalation for the treatment of inflammatory lung diseases like COPD.

Keywords: Calu-3; Inflammation; Inhalation; Oxidation; Resveratrol; Spray-dried.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Desiccation
  • Dry Powder Inhalers
  • Epithelial Cells / drug effects
  • Free Radical Scavengers / pharmacology
  • Humans
  • Interleukin-8 / biosynthesis
  • Lipopolysaccharides / biosynthesis
  • Particle Size
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Resveratrol
  • Stilbenes / administration & dosage*
  • Stilbenes / pharmacology*
  • Stress, Physiological
  • Transforming Growth Factor beta1 / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Free Radical Scavengers
  • Interleukin-8
  • Lipopolysaccharides
  • Stilbenes
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Resveratrol