Ultrasound-responsive nanobubbles for enhanced intravitreal drug migration: An ex vivo evaluation.

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dc.contributor.author Thakur, Sachin en
dc.contributor.author Chen, Ying-Shan en
dc.contributor.author Houston, Zachary H en
dc.contributor.author Fletcher, Nicholas en
dc.contributor.author Barnett, Nigel L en
dc.contributor.author Thurecht, Kristofer J en
dc.contributor.author Rupenthal, Ilva en
dc.contributor.author Parekh, Harendra S en
dc.date.accessioned 2019-06-13T02:45:11Z en
dc.date.issued 2019-03 en
dc.identifier.issn 0939-6411 en
dc.identifier.uri http://hdl.handle.net/2292/47009 en
dc.description.abstract The intravitreal route faces many challenges in rapidly and effectively reaching posterior eye pathology, with administered therapeutics experiencing non-specific distribution around and premature clearance from ocular tissues. Nanobubbles and ultrasound may improve outcomes of intravitreally administered drugs by influencing the directionality of drug-containing particle migration. In this study, we assessed the impact of trans-scleral or corneal ultrasound application on the distribution of intravitreally-injected nanobubbles. Rhodamine-tagged gas entrapped nanobubble formulations were prepared and injected into ex vivo bovine and porcine eyes and subjected to ultrasound (1 MHz, 0-2.5 W/cm2, 50-100% duty, 60 s). Bovine eyes were partially dissected to visualize the vitreous humor and particle migration was evaluated via optical fluorescence spectroscopy. Directional migration in porcine eyes was evaluated using a snap freezing protocol complemented by quantification of regional fluorescence. The impact on nanobubble migration following pars-plana injection and sequential ultrasound cycle application from scleral or corneal-surface positions was also assessed. Administration of ultrasound significantly enhanced the directional migration of nanobubbles in both ex vivo models, with multiple corneal ultrasound cycles promoting greater migration of dye-filled nanobubbles to posterior regions of the vitreous. Moreover, particles moved in a directional manner away from the ultrasound wave source demonstrating an ability to effectively control the rate and path of nanobubble migration. These findings establish an encouraging new and safe modality enabling rapid distribution of intravitreally-injected therapeutics where expeditious therapeutic intervention is warranted. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Vitreous Body en
dc.subject Animals en
dc.subject Cattle en
dc.subject Swine en
dc.subject Fluorescent Dyes en
dc.subject Drug Delivery Systems en
dc.subject Spectrometry, Fluorescence en
dc.subject Nanocapsules en
dc.subject Intravitreal Injections en
dc.subject Ultrasonic Waves en
dc.title Ultrasound-responsive nanobubbles for enhanced intravitreal drug migration: An ex vivo evaluation. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.ejpb.2019.01.014 en
pubs.begin-page 102 en
pubs.volume 136 en
dc.rights.holder Copyright: The author en
pubs.end-page 107 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Journal Article en
pubs.elements-id 760307 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Pharmacy en
pubs.org-id School of Medicine en
pubs.org-id Ophthalmology Department en
dc.identifier.eissn 1873-3441 en
pubs.record-created-at-source-date 2019-01-21 en
pubs.dimensions-id 30660691 en

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