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Sustained zero-orde...
Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions
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- Ahrenstedt, Lage (author)
- KTH,Cardiovascular Research Unit, University of Cape Town, South Africa
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- Hed, Yvonne (author)
- KTH,Ytbehandlingsteknik
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- Hult, Anders (author)
- KTH,Ytbehandlingsteknik
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- Zilla, Peter (author)
- Cardiovascular Research Unit, University of Cape Town, South Africa
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- Bezuidenhout, Deon (author)
- Cardiovascular Research Unit, University of Cape Town, South Africa
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- Malkoch, Michael, 1974- (author)
- KTH,Ytbehandlingsteknik
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(creator_code:org_t)
- Elsevier BV, 2024
- 2024
- English.
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In: Journal of Drug Delivery Science and Technology. - : Elsevier BV. - 1773-2247. ; 95
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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