Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis

Zara Sheikh, Larissa Gomes Dos Reis, Peta Bradbury, Giulio Meneguzzo, Santo Scalia, Paul M. Young, Hui Xin Ong*, Daniela Traini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Anti-inflammatory treatment options for cystic fibrosis (CF) patients are currently limited and as such, there is an imperative need to develop new anti-inflammatory agents to reduce the persistent inflammation present within CF lungs. This study explored the potential of Diclofenac (DICLO) as a novel inhaled anti-inflammatory drug for CF treatment. The anti-inflammatory activity of DICLO on an air–liquid interface (ALI) cell culture model of healthy (NuLi-1) and CF (CuFi-1) airways showed a significant reduction in the secretion of pro-inflammatory cytokines, IL-6 and IL-8. Therefore, pressurized metered dose inhaler (pMDI) DICLO formulations were developed to allow targeted DICLO delivery to CF airways. As such, two pMDI DICLO formulations with varying ethanol concentrations: 5% (w/w) equating to 150 µg of DICLO per dose (Low dose), and 15% (w/w) equating to 430 µg of DICLO per dose (High dose) were developed and characterized to determine the optimum formulation. The Low dose pMDI DICLO formulation showed a significantly smaller particle diameter with uniform distribution resulting in a greater aerosol performance when compared to High dose formulation. Consequently, the Low dose pMDI DICLO formulation was further evaluated in terms of in vitro transport characteristics and anti-inflammatory activity. Importantly, the DICLO pMDI displayed anti-inflammatory activity in both healthy and CF in vitro models, highlighting the potential of an aerosolized low-dose DICLO formulation as a promising inhaled anti-inflammatory therapy for CF treatment.

Original languageEnglish
Article number120319
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume596
DOIs
Publication statusPublished - 1 Mar 2021
Externally publishedYes

Keywords

  • Anti-inflammatory
  • Cystic fibrosis
  • Diclofenac
  • Inhaled
  • pMDI
  • Transport

Fingerprint

Dive into the research topics of 'Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis'. Together they form a unique fingerprint.

Cite this