Protective Abilities of an Inhaled DPI Formulation Based on Sodium Hyaluronate against Environmental Hazards Targeting the Upper Respiratory Tract

Juhura G Almazi; Dina M Silva; Valentina Trotta; Walter Fiore; Hui X Ong; Daniela Traini

doi:10.3390/pharmaceutics14071323

Protective Abilities of an Inhaled DPI Formulation Based on Sodium Hyaluronate against Environmental Hazards Targeting the Upper Respiratory Tract

Pharmaceutics. 2022 Jun 22;14(7):1323. doi: 10.3390/pharmaceutics14071323.

Authors

Juhura G Almazi^{1

2}, Dina M Silva², Valentina Trotta³, Walter Fiore⁴, Hui X Ong^{1

2

5}, Daniela Traini^{1

2

5}

Affiliations

¹ Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
² Ab Initio Pharma Pte Ltd., 63-73 Missenden Road, Camperdown, NSW 2050, Australia.
³ HollyCon Italy Pte Ltd., Srl, Via Danimarca 21, 20083 Gaggiano, Italy.
⁴ SOFAR Spa, Via Firenze, 40, 20060 Trezzano Rosa, Italy.
⁵ Macquarie Medical School, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia.

Abstract

The exposure of lung epithelium to environmental hazards is linked to several chronic respiratory diseases. We assessed the ability of an inhaled dry powder (DPI) medical device product (PolmonYDEFENCE/DYFESA^TM, SOFAR SpA, Trezzano Rosa, Italy), using a formulation of sodium hyaluronate (Na-Hya) as the key ingredient as a defensive barrier to protect the upper respiratory tract. Specifically, it was evaluated if the presence of the barrier formed by sodium hyaluronate present on the cells, reducing direct contact of the urban dust (UD) with the surface of cells can protect them in an indirect manner by the inflammatory and oxidative process started in the presence of the UD. Cytotoxicity and the protection capability against the oxidative stress of the product were tested in vitro using Calu-3 cells exposure to UD as a trigger for oxidative stress. Inflammation and wound healing were assessed using an air-liquid interface (ALI) culture model of the Calu-3 cells. Deposition studies of the formulation were conducted using a modified Anderson cascade impactor (ACI) and the monodose PillHaler^® dry powder inhaler (DPI) device, Na-Hya was detected and quantified using high-performance-liquid-chromatography (HPLC). Solubilised PolmonYDEFENCE/DYFESA^TM gives protection against oxidative stress in Calu-3 cells in the short term (2 h) without any cytotoxic effects. ALI culture experiments, testing the barrier-forming (non-solubilised) capabilities of PolmonYDEFENCE/DYFESA^TM, showed that the barrier layer reduced inflammation triggered by UD and the time for wound closure compared to Na-Hya alone. Deposition experiments using the ACI and the PillHaler^® DPI device showed that the majority of the product was deposited in the upper part of the respiratory tract. Finally, the protective effect of the product was efficacious for up to 24 h without affecting mucus production. We demonstrated the potential of PolmonYDEFENCE/DYFESA^TM as a preventative barrier against UD, which may aid in protecting the upper respiratory tract against environmental hazards and help with chronic respiratory diseases.

Keywords: air-liquid interface; barrier; dry powder inhaler; protection; sodium hyaluronate.

Grants and funding

This research was funded by SOFAR Spa. D.T. is funded by an NHMRC grant APP1173363.