Faculty of Medical and Health Sciences


BOTU Research Projects


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The Buchanan Ocular Therapeutics Unit (BOTU) aims to develop and translate ocular therapeutic related scientific research into the clinical setting whether pharmaceutical-, cell-, or technology-based. Current research focusses on the development of stimuli-responsive ocular implants that are able to slowly release the drug over time, while also allowing for non-invasive top-up dosing based on individual patient needs. Moreover, the Unit is evaluating novel drug therapies for the treatment of sight-threatening diseases such as age-related macular degeneration and diabetic retinopathy.

Find out more about our current projects:

Students looking for a research project in Ophthalmology should try searching on the Finda Thesis website for currently available projects.

Conducting polymer based scleral implant


In this project we are aiming to develop a scleral implant based on a porous conducting polymer that is able to provide tuneable drug release (based on the disease progression) over prolonged periods of time by application of a small electrical stimulus, thus resulting in more efficacious and patient-friendly treatment. In addition, we are investigating the pressure sensing capability of such porous conducting polymer structures with the ultimate aim to create a self-regulating implant including wireless power technology for optimal glaucoma management.

Funding

This project is funded by the Health Research Council of New Zealand [14/018], the Buchanan Charitable Foundation, and the University of Auckland Faculty of Medical and Health Sciences (FRDF).

Key staff and students

Schematic of implant location and drug release
Schematic of implant location and drug release.
SEM image of honeycomb PEDOT structure made via vapour phase polymerization.
SEM image of honeycomb PEDOT structure made via vapour phase polymerization.

Project outputs

Journal articles: 

  • Yasin MN, Svirskis D, Seyfoddin A, Rupenthal ID 2014. Implants for drug delivery to the posterior segment of the eye: A focus on stimuli-responsive and tunable release systems. J Control Release 196:208-221
  • Seyfoddin A, Chan A, Chen WT, Rupenthal ID, Waterhouse GI, Svirskis D 2015. Electro-responsive macroporous polypyrrole scaffolds for triggered dexamethasone delivery. Eur J Pharm Biopharm 94:419-426
  • Ramtin A, Seyfoddin A, Coutinho FP, Waterhouse GI, Rupenthal ID, Svirskis D 2016. Cytotoxicity considerations and electrically tunable release of dexamethasone from polypyrrole for the treatment of back-of-the-eye conditions. Drug Deliv Transl Res 6:793-799
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Light-responsive intravitreal implant


In this project we aim to shine light into the eye to either solidify or activate an intravitreal implant to allow for sustained and controlled drug dosing. The light-cured implant is based on a modified polymer containing drug-loaded nanoparticles, while the light-activated system comprises barrier arm controlled microparticles.

Peptide-loaded polymeric nanoparticles.
Light-responsive drug release from porous microparticles.

Funding

This project is funded by the Health Research Council of New Zealand [14/018].

Key staff and students

Project outputs

Journal articles:

  • Bisht R, Jaiswal JK, Chen YS, Jin J, Rupenthal ID 2016. Light-responsive in situ forming injectable implants for effective drug delivery to the posterior segment of the eye. Expert Opin Drug Deliv 13:953-962
  • Bisht R, Jaiswal JK, Rupenthal ID 2017. Nanoparticle-loaded biodegradable light-responsive in situ forming injectable implants for effective peptide delivery to the posterior segment of the eye. Med Hypotheses 103:5-9
  • Bisht R, Jaiswal JK, Oliver VF, Eurtivong C, Reynisson J, Rupenthal ID 2017. Preparation and evaluation of PLGA nanoparticle-loaded biodegradable light-responsive injectable implants as a promising platform for intravitreal drug delivery. J Drug Deliv Sci Tec 40:142-56
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Ultrasound mediated ocular drug delivery


This project investigates the use of ultrasound to improve the delivery of drugs to the retinal tissues by cavitation and acoustic streaming. A peptide drug is loaded into nanoparticle coated with hyaluronan for active targeting to retinal cells and delivery efficacy is tested with and without application of ultrasound. 

Key staff and students

Project outputs

Journal article:

  • Huang D, Chen YS, Rupenthal ID 2017. Overcoming ocular drug delivery barriers through the use of physical forces. Adv Drug Deliv Rev
  • Huang D, Chen YS, Thakur SS, Rupenthal ID 2017. Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection. Eur J Pharm Biopharm 119:125-136
  • Huang D, Chen YS, Rupenthal ID 2017. Hyaluronic Acid Coated Albumin Nanoparticles for Targeted Peptide Delivery to the RetinaMol Pharm 14:533-545
Ultrasound mediated ocular drug delivery
Ultrasound enhances nanoparticle distribution in the posterior segment of the eye. (Click to view larger version.)
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Vascular breakdown in diabetic retinopathy


This project investigates the role of connexin43 in the loss of vascular integrity associated with diabetic retinopathy. Connexin expression is being characterised in human donor tissue and compared to expression in a model of diabetic retinopathy, which will be used to investigate novel treatments for this sight-threatening disease.

Funding

This project is funded by the Buchanan Charitable Foundation.

Key staff and students

Project outputs

Published conference proceedings:


 

Connexin43 expression in retinal pigment epithelium cells.
Connexin43 expression in retinal pigment epithelium cells.


 

Connexin43 (green) and glial fibrillary acidic protein (GFAP, red) expression in the Akimba mouse retina.
Connexin43 (green) and GFAP (red) expression in Akimba mouse retina.
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Cell penetrating peptide for ocular drug delivery


This project investigates the use of the fusion peptide XG19, a cell penetrating, intracellularly acting Connexin43 hemichannel blocker, as a potential therapeutic for neovascular age-related macular degeneration. XG19 targets primarily hypoxic cells and is not sequestered by red blood cells enabling low dose delivery yet treatment efficacy. A mouse model of laser-induced CNV is currently being optimised to assess the peptide efficacy in vivo.

Funding

This project is funded by Buchanan Charitable Foundation.
 

Key staff and students

Project outputs

Patents:

XG19 uptake in cultured retinal pigment epithelium cells
XG19 uptake in cultured retinal pigment epithelium cells
Fundus fluorescein angiography image of mouse retina post laser induction (acquired using the Micron IV)
Fundus fluorescein angiography image of mouse retina post laser induction (acquired using the Micron IV)
  • Coutinho FP, Rupenthal ID, Green CR 2017. Novel constructs and methods of treatment. New Zealand Provisional Patent Application No. 731353
  • Coutinho FP, Rupenthal ID, Green CR 2017. Methods of treatment. New Zealand Provisional Patent Application No. 731364
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Ex vivo ocular penetration model


This project aims to develop an ex vivo model to evaluate the penetration of various formulations into the ocular tissues after topical application. Such a model allows screening of ocular formulations at an early stage of development and could reduce the cost and complexity of testing routines currently used by the pharmaceutical industry. Dieter Scherer, PhD, CSO Novaliq says: “Industry needs a reliable model to test formulations already at an early stage. We are very happy to work together with such an experienced group in the area of ocular drug delivery.”

Funding

This project is funded by Novaliq GmbH.
 

Key staff and students

 

 

Ex vivo whole eye model for ocular penetration studies
Ex vivo whole eye model for ocular penetration studies.
Penetration of a lipophilic dye (red) into porcine cornea (blue nuclear stain).
Penetration of a lipophilic dye (red) into porcine cornea (blue nuclear stain).

Project outputs

Journal articles:

Published conference proceedings:
  • Agarwal P, Scherer D, Günther B, Rupenthal ID 2016. Semi-fluorinated alkanes for topical delivery of Cyclosporine AActa Ophthalmol 94:s256
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In vitro modelling of intraocular drug distribution


In this project, we are developing a model that will help predict the pharmacokinetics of therapeutic formulations inside the eye. The model will be built to match intraocular human geometry and physiology and will allow us to perform intravitreal drug elimination studies in an in vitro set up. The low cost, reusability and ability to undertake evaluations devoid of ethical constraints make this approach a desirable alternative to current in vivo models.

Funding

This project is funded by Buchanan Charitable Foundation and the University of Auckland Faculty of Medical and Health Sciences (FRDF).

Key staff and students

Design of in vitro eye matching human intraocular dimensions
Design of in vitro eye matching human intraocular dimensions
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UV light responsive periocular implant


This project uses UV light to trigger in situ formation of a collagen-based implant. The polymer solution containing suitable quantum dots is injected into the periocular space after which it is subjected to UV light. This results in the formation of a biodegradable gel implant which will sustain the release of contained therapeutics to the posterior eye.

Funding

This project is funded by the Buchanan Charitable Foundation and the Leather and Shoe Research Association.

Key staff and students

Collagen after UV treatment
Collagen after UV treatment
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