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Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Awwad, S; Al-Shohani, A; Khaw, PT; Brocchini, S; (2018) Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels. Macromolecular Bioscience , 18 (2) , Article 1700255. 10.1002/mabi.201700255. Green open access

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Abstract

Hydrogels can potentially prolong the release of a therapeutic protein, especially to treat blinding conditions. One challenge is to ensure that the protein and hydrogel are intimately mixed by better protein entanglement within the hydrogel. N-isopropylacrylamide (NIPAAM) gels are optimized with poly(ethylene glycol) diacrylate (PEDGA) crosslinker in the presence of either bevacizumab or PEG conjugated ranibizumab (PEG10-Fabrani). The release profiles of the hydrogels are evaluated using an outflow model of the eye, which is previously validated for human clearance of proteins. Release kinetics of in situ loaded bevacizumab-NIPAAM gels displays a prolonged bimodal release profile in phosphate buffered saline compared to bevacizumab loaded into a preformed NIPAAM gel. Bevacizumab release in simulated vitreous from in situ loaded gels is similar to bevacizumab control indicating that diffusion through the vitreous rather than from the gel is rate limiting. Ranibizumab is site-specifically PEGylated by disulfide rebridging conjugation. Prolonged and continuous release is observed with the in situ loaded PEG10-Fabrani-NIPAAM gels compared to PEG10-Fabrani injection (control). Compared to an unmodified protein, there is better mixing due to PEG entanglement and compatibility of PEG10-Fabrani within the NIPAAM-PEDGA hydrogel. These encouraging results suggest that the extended release of PEGylated proteins in the vitreous can be achieved using injectable hydrogels.

Type: Article
Title: Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/mabi.201700255
Publisher version: https://doi.org/10.1002/mabi.201700255
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Hydrogel; ocular delivery; PEGylated protein; stimuli responsive; therapeutic protein
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
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
URI: https://discovery.ucl.ac.uk/id/eprint/10039435
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