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Conference Paper: In vivo evaluation of hyaluronic acid based in situ hydrogel for prolonged release of Avastin by intravitreal injection

TitleIn vivo evaluation of hyaluronic acid based in situ hydrogel for prolonged release of Avastin by intravitreal injection
Authors
Keywords748 vascular endothelial growth factor
763 vitreous
561 injection
Issue Date2014
PublisherThe Association for Research in Vision and Ophthalmology (ARVO).
Citation
The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Orlando, USA, 4-8 May 2014, abstract no. 5261-C0057 How to Cite?
AbstractPurpose: To evaluate the biocompatibility and 6 months in vivo release of Avastin from a hyaluronic acid based in situ hydrogel after intravitreal injection in rabbit eye. Methods: The in situ hydrogel is formed by the chemical crosslinking of two polymer solutions, the vinylsulfonate hyaluronic acid (HA-VS) and thiolated dextran (Dex-SH) using catalyst-free click chemistry in aqueous phase (Yu and Chau 2012). The pH 7.4 buffered HA-VS, Dex-SH and Avastin were mixed on ice and injected to the vitreous of rabbits with 30 G needle. The biocompatibility was evaluated by binocular indirect ophthalmoscope (BIO), full-field ERG and histology at various time points from 1 week to 3 months. The concentrations of both total and active Avastin in rabbit vitreous were determined by ELISA assay. Results: A transparent gel is seen in the vitreous after injection. The low viscosity of the mixture made injection easy even through 30G needle, and the fast gelation at body temperature (<10 seconds) ensure almost immediately gelation after injection. BIO images, ERG and histology showed that the gel does not induce hemorrhage, retinal detachment, inflammation or other gross pathological changes in rabbit eye after injection (figure 1). While the bolus intravitreal injection of native Avastin follows the first order elimination kinetics in rabbit eye, the in situ gel formation was able to extend the retention of Avastin in rabbit eye above therapeutic concentration for at least 6 months (figure 2). The concentration of Avastin 3 months and 6 months after injection was 100 and 109 times higher than bolus injection after the same period of time. Conclusions: The new in situ hydrogel formulation of Avastin was transparent, biocompatible and able to prolong the retention of drug in rabbit eye in vivo for at least 6 months.
DescriptionConference Theme: Leading Eye and Vision Research
Session 477: Drug delivery #2
Persistent Identifierhttp://hdl.handle.net/10722/199842

 

DC FieldValueLanguage
dc.contributor.authorChau, Yen_US
dc.contributor.authorYu, Yen_US
dc.contributor.authorLau, CMLen_US
dc.contributor.authorLo, ACYen_US
dc.date.accessioned2014-07-22T01:41:35Z-
dc.date.available2014-07-22T01:41:35Z-
dc.date.issued2014en_US
dc.identifier.citationThe Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Orlando, USA, 4-8 May 2014, abstract no. 5261-C0057en_US
dc.identifier.urihttp://hdl.handle.net/10722/199842-
dc.descriptionConference Theme: Leading Eye and Vision Research-
dc.descriptionSession 477: Drug delivery #2-
dc.description.abstractPurpose: To evaluate the biocompatibility and 6 months in vivo release of Avastin from a hyaluronic acid based in situ hydrogel after intravitreal injection in rabbit eye. Methods: The in situ hydrogel is formed by the chemical crosslinking of two polymer solutions, the vinylsulfonate hyaluronic acid (HA-VS) and thiolated dextran (Dex-SH) using catalyst-free click chemistry in aqueous phase (Yu and Chau 2012). The pH 7.4 buffered HA-VS, Dex-SH and Avastin were mixed on ice and injected to the vitreous of rabbits with 30 G needle. The biocompatibility was evaluated by binocular indirect ophthalmoscope (BIO), full-field ERG and histology at various time points from 1 week to 3 months. The concentrations of both total and active Avastin in rabbit vitreous were determined by ELISA assay. Results: A transparent gel is seen in the vitreous after injection. The low viscosity of the mixture made injection easy even through 30G needle, and the fast gelation at body temperature (<10 seconds) ensure almost immediately gelation after injection. BIO images, ERG and histology showed that the gel does not induce hemorrhage, retinal detachment, inflammation or other gross pathological changes in rabbit eye after injection (figure 1). While the bolus intravitreal injection of native Avastin follows the first order elimination kinetics in rabbit eye, the in situ gel formation was able to extend the retention of Avastin in rabbit eye above therapeutic concentration for at least 6 months (figure 2). The concentration of Avastin 3 months and 6 months after injection was 100 and 109 times higher than bolus injection after the same period of time. Conclusions: The new in situ hydrogel formulation of Avastin was transparent, biocompatible and able to prolong the retention of drug in rabbit eye in vivo for at least 6 months.-
dc.languageengen_US
dc.publisherThe Association for Research in Vision and Ophthalmology (ARVO).-
dc.relation.ispartofAnnual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)en_US
dc.subject748 vascular endothelial growth factor-
dc.subject763 vitreous-
dc.subject561 injection-
dc.titleIn vivo evaluation of hyaluronic acid based in situ hydrogel for prolonged release of Avastin by intravitreal injectionen_US
dc.typeConference_Paperen_US
dc.identifier.emailLau, CML: lcmlau@hku.hken_US
dc.identifier.emailLo, ACY: amylo@hkucc.hku.hken_US
dc.identifier.authorityLo, ACY=rp00425en_US
dc.identifier.hkuros230941en_US
dc.publisher.placeUnited States-

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