Combination of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate for the treatment of inflammatory lung diseases: An in vitro study

Arianna Fallacara; Laura Busato; Michele Pozzoli; Maliheh Ghadiri; Hui Xin Ong; Paul M Young; Stefano Manfredini; Daniela Traini

doi:10.1016/j.ejps.2018.04.042

Combination of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate for the treatment of inflammatory lung diseases: An in vitro study

Eur J Pharm Sci. 2018 Jul 30:120:96-106. doi: 10.1016/j.ejps.2018.04.042. Epub 2018 Apr 30.

Authors

Arianna Fallacara¹, Laura Busato², Michele Pozzoli³, Maliheh Ghadiri⁴, Hui Xin Ong⁵, Paul M Young⁶, Stefano Manfredini⁷, Daniela Traini⁸

Affiliations

¹ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy.. Electronic address: fllrnn@unife.it.
² Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia; Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy.. Electronic address: laura01.busato@student.unife.it.
³ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia. Electronic address: michele.pozzoli@sydney.edu.au.
⁴ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia. Electronic address: maliheh.ghadiri@sydney.edu.au.
⁵ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia. Electronic address: ong.hui@sydney.edu.au.
⁶ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia. Electronic address: paul.young@sydney.edu.au.
⁷ Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy.. Electronic address: mv9@unife.it.
⁸ Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, 431 Glebe Point Road, Glebe, NSW 2037, Australia. Electronic address: daniela.traini@sydney.edu.au.

PMID: 29723596
DOI: 10.1016/j.ejps.2018.04.042

Abstract

This in vitro study evaluated, for the first time, the safety and the biological activity of a novel urea-crosslinked hyaluronic acid component and sodium ascorbyl phosphate (HA-CL - SAP), singularly and/or in combination, intended for the treatment of inflammatory lung diseases. The aim was to understand if the combination HA-CL - SAP had an enhanced activity with respect to the combination native hyaluronic acid (HA) - SAP and the single SAP, HA and HA-CL components. Sample solutions displayed pH, osmolality and viscosity values suitable for lung delivery and showed to be not toxic on epithelial Calu-3 cells at the concentrations used in this study. The HA-CL - SAP displayed the most significant reduction in interleukin-6 (IL-6) and reactive oxygen species (ROS) levels, due to the combined action of HA-CL and SAP. Moreover, this combination showed improved cellular healing (wound closure) with respect to HA - SAP, SAP and HA, although at a lower rate than HA-CL alone. These preliminary results showed that the combination HA-CL - SAP could be suitable to reduce inflammation and oxidative stress in lung disorders like acute respiratory distress syndrome, asthma, emphysema and chronic obstructive pulmonary disease, where inflammation is prominent.

Keywords: Anti-inflammatory; Antioxidant; Hyaluronic acid; Sodium ascorbyl phosphate; Urea-crosslinked hyaluronic acid; Wound healing.

MeSH terms

Anti-Inflammatory Agents / administration & dosage
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / toxicity
Antioxidants / administration & dosage
Antioxidants / chemistry*
Antioxidants / toxicity
Ascorbic Acid / administration & dosage
Ascorbic Acid / analogs & derivatives*
Ascorbic Acid / chemistry
Ascorbic Acid / toxicity
Cell Line, Tumor
Cell Survival / drug effects
Cross-Linking Reagents / chemistry*
Dose-Response Relationship, Drug
Drug Combinations
Drug Compounding
Electric Impedance
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Humans
Hyaluronic Acid / administration & dosage
Hyaluronic Acid / chemistry*
Hyaluronic Acid / toxicity
Hydrogen-Ion Concentration
Interleukin-6 / metabolism
Lung / drug effects*
Lung / metabolism
Lung / pathology
Lung Diseases, Obstructive / drug therapy*
Lung Diseases, Obstructive / metabolism
Lung Diseases, Obstructive / pathology
Osmolar Concentration
Reactive Oxygen Species / metabolism
Technology, Pharmaceutical / methods
Urea / chemistry*
Viscosity

Substances

Anti-Inflammatory Agents
Antioxidants
Cross-Linking Reagents
Drug Combinations
IL6 protein, human
Interleukin-6
Reactive Oxygen Species
ascorbate-2-phosphate
Urea
Hyaluronic Acid
Ascorbic Acid