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Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions
KTH. Cardiovascular Research Unit, University of Cape Town, South Africa.ORCID iD: 0000-0001-8370-9637
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0001-9589-7479
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0002-9372-0829
Cardiovascular Research Unit, University of Cape Town, South Africa.
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2024 (English)In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 95, article id 105637Article in journal (Refereed) Published
Abstract [en]

Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.

Place, publisher, year, edition, pages
Elsevier BV , 2024. Vol. 95, article id 105637
National Category
Pharmaceutical Sciences
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URN: urn:nbn:se:kth:diva-345757DOI: 10.1016/j.jddst.2024.105637ISI: 001225572200001Scopus ID: 2-s2.0-85189810726OAI: oai:DiVA.org:kth-345757DiVA, id: diva2:1852533
Note

QC 20240603

Available from: 2024-04-18 Created: 2024-04-18 Last updated: 2024-06-03Bibliographically approved

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Hed, YvonneHult, AndersMalkoch, Michael

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