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Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery—A Particle Engineering Approach
Luleå University of Technology, Department of Engineering Sciences and Mathematics, Material Science. Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 75124 Uppsala, Sweden.ORCID iD: 0000-0002-4628-3857
Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, 75124 Uppsala, Sweden.ORCID iD: 0000-0001-8327-6755
Early Product Development & Manufacturing, Pharmaceutical Sciences, R&D, AstraZeneca, 43183 Gothenburg, Sweden.
Advanced Drug Delivery, Pharmaceutical Sciences, R&D, Astra Zeneca, 43183 Gothenburg, Sweden.
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2021 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 13, no 11, article id 1878Article in journal (Refereed) Published
Abstract [en]

Hydrogels warrant attention as a potential material for use in sustained pulmonary drug delivery due to their swelling and mucoadhesive features. Herein, hyaluronic acid (HA) is considered a promising material due to its therapeutic potential, the effect on lung inflammation, and possible utility as an excipient or drug carrier. In this study, the feasibility of using HA hydrogels (without a model drug) to engineer inhalation powders for controlled pulmonary drug delivery was assessed. A combination of chemical crosslinking and spray-drying was proposed as a novel methodology for the preparation of inhalation powders. Different crosslinkers (urea; UR and glutaraldehyde; GA) were exploited in the hydrogel formulation and the obtained powders were subjected to extensive characterization. Compositional analysis of the powders indicated a crosslinked structure of the hydrogels with sufficient thermal stability to withstand spray drying. The obtained microparticles presented a spherical shape with mean diameter particle sizes from 2.3 ± 1.1 to 3.2 ± 2.9 μm. Microparticles formed from HA crosslinked with GA exhibited a reasonable aerosolization performance (fine particle fraction estimated as 28 ± 2%), whereas lower values were obtained for the UR-based formulation. Likewise, swelling and stability in water were larger for GA than for UR, for which the results were very similar to those obtained for native (not crosslinked) HA. In conclusion, microparticles could successfully be produced from crosslinked HA, and the ones crosslinked by GA exhibited superior performance in terms of aerosolization and swelling.

Place, publisher, year, edition, pages
MDPI, 2021. Vol. 13, no 11, article id 1878
Keywords [en]
hyaluronic acid, salbutamol sulphate, spray-drying, urea, glutaraldehyde, drug delivery
National Category
Polymer Chemistry
Research subject
Engineering Materials
Identifiers
URN: urn:nbn:se:ltu:diva-88012DOI: 10.3390/pharmaceutics13111878ISI: 000726994300001PubMedID: 34834293Scopus ID: 2-s2.0-85118747181OAI: oai:DiVA.org:ltu-88012DiVA, id: diva2:1614302
Funder
Vinnova, 2017-02690; 2019-00048Vinnova
Note

Validerad;2021;Nivå 2;2021-11-25 (beamah)

Available from: 2021-11-25 Created: 2021-11-25 Last updated: 2021-12-13Bibliographically approved

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Nikjoo, Dariush

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