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

Sheikh, Z; Gomes Dos Reis, L; Bradbury, P; Meneguzzo, G; Scalia, S; Young, PM; Ong, HX; Traini, D

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

Sheikh, Z Gomes Dos Reis, L Bradbury, P

Meneguzzo, G Scalia, S Young, PM Ong, HX Traini, D

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Publisher:: ELSEVIER
Publication Type:: Journal Article
Citation:: Int J Pharm, 2021, 596, pp. 120319
Issue Date:: 2021-03-01

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Field	Value	Language
dc.contributor.author	Sheikh, Z
dc.contributor.author	Gomes Dos Reis, L
dc.contributor.author	Bradbury, P https://orcid.org/0000-0001-6360-9591
dc.contributor.author	Meneguzzo, G
dc.contributor.author	Scalia, S
dc.contributor.author	Young, PM
dc.contributor.author	Ong, HX
dc.contributor.author	Traini, D
dc.date.accessioned	2022-04-14T20:36:47Z
dc.date.available	2021-01-23
dc.date.available	2022-04-14T20:36:47Z
dc.date.issued	2021-03-01
dc.identifier.citation	Int J Pharm, 2021, 596, pp. 120319
dc.identifier.issn	0378-5173
dc.identifier.issn	1873-3476
dc.identifier.uri	http://hdl.handle.net/10453/156269
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER
dc.relation.ispartof	Int J Pharm
dc.relation.isbasedon	10.1016/j.ijpharm.2021.120319
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Pharmacology & Pharmacy
dc.subject.mesh	Administration, Inhalation
dc.subject.mesh	Anti-Inflammatory Agents
dc.subject.mesh	Bronchodilator Agents
dc.subject.mesh	Cystic Fibrosis
dc.subject.mesh	Diclofenac
dc.subject.mesh	Humans
dc.subject.mesh	Metered Dose Inhalers
dc.subject.mesh	Nebulizers and Vaporizers
dc.subject.mesh	Humans
dc.subject.mesh	Cystic Fibrosis
dc.subject.mesh	Diclofenac
dc.subject.mesh	Bronchodilator Agents
dc.subject.mesh	Anti-Inflammatory Agents
dc.subject.mesh	Administration, Inhalation
dc.subject.mesh	Nebulizers and Vaporizers
dc.subject.mesh	Metered Dose Inhalers
dc.title	Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis.
dc.type	Journal Article
utslib.citation.volume	596
utslib.location.activity	Netherlands
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
dc.date.updated	2022-04-14T20:36:46Z
pubs.publication-status	Published
pubs.volume	596

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.

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http://hdl.handle.net/10453/156269