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

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Jul 27

PMID 35890219

Authors

Juhura G Almazi

Dina M Silva

Valentina Trotta

Walter Fiore

Hui X Ong

Daniela Traini

Affiliations

Soon will be listed here.

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, 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 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, 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 as a preventative barrier against UD, which may aid in protecting the upper respiratory tract against environmental hazards and help with chronic respiratory diseases.

References

Garantziotis S, Brezina M, Castelnuovo P, Drago L . The role of hyaluronan in the pathobiology and treatment of respiratory disease. Am J Physiol Lung Cell Mol Physiol. 2016; 310(9):L785-95. PMC: 4867348. DOI: 10.1152/ajplung.00168.2015. View

Dhooghe B, Noel S, Huaux F, Leal T . Lung inflammation in cystic fibrosis: pathogenesis and novel therapies. Clin Biochem. 2014; 47(7-8):539-46. DOI: 10.1016/j.clinbiochem.2013.12.020. View

Onodera Y, Teramura T, Takehara T, Fukuda K . Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes. FEBS Open Bio. 2015; 5:476-84. PMC: 4475775. DOI: 10.1016/j.fob.2015.05.007. View

Rogueda P . HPFP, a model propellant for pMDIs. Drug Dev Ind Pharm. 2003; 29(1):39-49. DOI: 10.1081/ddc-120016682. View

Kaialy W, Martin G, Ticehurst M, Momin M, Nokhodchi A . The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient. Int J Pharm. 2010; 392(1-2):178-88. DOI: 10.1016/j.ijpharm.2010.03.057. View

Haghi M, Young P, Traini D . A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across Air Interface Respiratory Epithelia. AAPS PharmSciTech. 2018; 19(7):3272-3276. DOI: 10.1208/s12249-018-1170-5. View

Kleniewska P, Pawliczak R . The participation of oxidative stress in the pathogenesis of bronchial asthma. Biomed Pharmacother. 2017; 94:100-108. DOI: 10.1016/j.biopha.2017.07.066. View

Hertel N, Birk G, Scherliess R . Performance tuning of particle engineered mannitol in dry powder inhalation formulations. Int J Pharm. 2020; 586:119592. DOI: 10.1016/j.ijpharm.2020.119592. View

Traboulsi H, Guerrina N, Iu M, Maysinger D, Ariya P, Baglole C . Inhaled Pollutants: The Molecular Scene behind Respiratory and Systemic Diseases Associated with Ultrafine Particulate Matter. Int J Mol Sci. 2017; 18(2). PMC: 5343780. DOI: 10.3390/ijms18020243. View

10.

Shteyngart B, Chaiwiriyakul S, Wong J, Cantor J . Preferential binding of lysozyme to elastic fibres in pulmonary emphysema. Thorax. 1998; 53(3):193-6. PMC: 1745169. DOI: 10.1136/thx.53.3.193. View

11.

Rincon M, Irvin C . Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci. 2012; 8(9):1281-90. PMC: 3491451. DOI: 10.7150/ijbs.4874. View

12.

Croasdell Lucchini A, Gachanja N, Rossi A, Dorward D, Lucas C . Epithelial Cells and Inflammation in Pulmonary Wound Repair. Cells. 2021; 10(2). PMC: 7914803. DOI: 10.3390/cells10020339. View

13.

Nyman E, Henricson J, Ghafouri B, Anderson C, Kratz G . Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model. Plast Reconstr Surg Glob Open. 2019; 7(5):e2221. PMC: 6571313. DOI: 10.1097/GOX.0000000000002221. View

14.

MacNee W . Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol. 2001; 429(1-3):195-207. DOI: 10.1016/s0014-2999(01)01320-6. View

15.

Haghi M, Young P, Traini D, Jaiswal R, Gong J, Bebawy M . Time- and passage-dependent characteristics of a Calu-3 respiratory epithelial cell model. Drug Dev Ind Pharm. 2010; 36(10):1207-14. DOI: 10.3109/03639041003695113. View

16.

Toole B . Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004; 4(7):528-39. DOI: 10.1038/nrc1391. View

17.

Ong H, Jackson C, Cole J, Lackie P, Traini D, Young P . Primary Air-Liquid Interface Culture of Nasal Epithelium for Nasal Drug Delivery. Mol Pharm. 2016; 13(7):2242-52. DOI: 10.1021/acs.molpharmaceut.5b00852. View

18.

Sun J, Yu J, Shen Z, Niu X, Wang D, Wang X . Oxidative stress-inducing effects of various urban PM road dust on human lung epithelial cells among 10 Chinese megacities. Ecotoxicol Environ Saf. 2021; 224:112680. DOI: 10.1016/j.ecoenv.2021.112680. View

19.

Moldoveanu B, Otmishi P, Jani P, Walker J, Sarmiento X, Guardiola J . Inflammatory mechanisms in the lung. J Inflamm Res. 2011; 2:1-11. PMC: 3218724. View

20.

Maiz Carro L, Martinez-Garcia M . Use of Hyaluronic Acid (HA) in Chronic Airway Diseases. Cells. 2020; 9(10). PMC: 7601363. DOI: 10.3390/cells9102210. View