Ma, Yingchang;
Yu, Ziqi;
Waudby, Christopher A;
Ju, Tian;
Zhou, Xintong;
Brocchini, Steve;
Williams, Gareth R;
(2024)
Development of hyaluronic acid/β-cyclodextrin semi-interpenetrating network hydrogels for prolonged delivery of water-soluble drug sunitinib malate.
International Journal of Pharmaceutics
, Article 125039. 10.1016/j.ijpharm.2024.125039.
(In press).
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Abstract
Sunitinib malate (SUM), widely used in cancer treatment for its anti-VEGF properties, has also been explored for ocular neovascular diseases. For ocular applications, sustained drug release is essential to reduce dosing frequency. Hyaluronic acid (HA)-based hydrogels are commonly used for controlled drug delivery, but their hydrophilicity leads to rapid drug diffusion, especially for water-soluble drugs like SUM. To address this, β-cyclodextrin (β-CD) polymers (2–300 kDa) were incorporated into tyramine-conjugated HA (HA-TA) (200–400 kDa) networks to extend drug release via host–guest inclusion complexes. SUM-CD intermolecular interactions were identified and characterised by 1H NMR and FTIR spectroscopies, and NOESY spectra further confirmed a 2 SUM: 1 βCD inclusion complex. β-CD polymers (10 % w/v) were integrated into HA-TA (0.25, 0.5, 1 % w/v) networks crosslinked through enzymatic crosslinking using horseradish peroxidase and hydrogen peroxide, forming a semi-interpenetrating polymer network hydrogel. This hydrogel exhibited faster gelation, enhanced swelling behaviour, higher drug loading capacity, a denser matrix, and a longer SUM release duration compared to HA-TA hydrogels. In an in vitro flow model, post-gelation loading of SUM led to a longer release duration than pre-loading, with release continuing over 20 days. The HA-CD semi-IPN hydrogel therefore warrants further exploration for its potential ocular applications.
| Type: | Article |
|---|---|
| Title: | Development of hyaluronic acid/β-cyclodextrin semi-interpenetrating network hydrogels for prolonged delivery of water-soluble drug sunitinib malate |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ijpharm.2024.125039 |
| Publisher version: | https://doi.org/10.1016/j.ijpharm.2024.125039 |
| Language: | English |
| Additional information: | This is an open access article distributed under the terms of the Creative Commons CC-BY license, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Hydrogel; Sustained release; Drug delivery system; Inclusion complex; β-cyclodextrin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10202644 |
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