Conducting Polymer Implant for On-demand Ocular Drug Delivery

Introduction: Implants have become an attractive treatment option for chronic posterior eye conditions. However, a patient’s disease state and any concurrent side-effects may require a dose adjustment which is not possible with currently marketed implants. Stimuli-responsive implants present an opportunity to tailor the release of the active. They may be composed of conducting polymers (CP) such as poly(3,4-ethylenedioxythiophene) (PEDOT), a robust CP with good biocompatibility and reproducible electroactivity. This thesis investigated the fabrication of a PEDOT-based system suitable for implantation to provide stimuli-responsive ocular drug delivery. Methods: PEDOT films (non-porous and porous) were fabricated via vapour phase polymerisation (VPP) and characterised for their surface morphology, electrochemical behaviour and biocompatibility. Dexamethasone phosphate (dexP) was loaded after polymerisation as a dopant via active and passive ion-exchange. DexP release was determined in the absence and presence of an electrical stimulus. Dexamethasone base (dex) was also physically entrapped into the pores of porous PEDOT and a sealing layer was polymerized on top. PEDOT-coated cellulose membranes, replicating the PEDOT sealing layer, were also fabricated and characterised for their drug permeability using Franz-cells. Finally, a prototype implant for in-vitro evaluation was fabricated by 3D printing the casing and placing drug loaded VPP PEDOT films inside. Results and Discussion: Porous PEDOT prepared by VPP exhibited a highly porous morphology and a three-fold higher electrochemically active surface area (as determined by cyclic voltammetry) compared to non-porous PEDOT prepared by VPP. Release medium extracts from non-porous and porous PEDOT films displayed no significant cytotoxicity. The amount of dexP loading achieved via active ion-exchange was almost three-fold higher compared to passive ion-exchange. The effect of redox state over dexP release was determined where a pulse stimulus released maximum amounts of drug. A faster rate of dexP release was observed for porous compared to non-porous films. Dex was physically entrapped into the pores to increase drug loading; however, it leaked through the PEDOT sealing layer within 1 h. PEDOT-coated cellulose membranes confirmed the high permeability of these sealing layers. Therefore, the assembled prototype implant contained only dexP loaded films and exhibited a burst in drug release during in-vitro stimulation aligning well with previous dexP release where a similar burst in drug release was observed upon the application of in-vitro stimulus. Conclusion: A PEDOT-based system suitable for implantation was fabricated exhibiting a stimuli-responsive burst in drug release. However, drug loading and retention need to be further improved such as by physical entrapment and effective sealing to achieve long-term on-demand drug delivery.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Ophthalmology

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2016

Author dc:creator

• Yasin, Muhammad Naveed

Advisors dc:contributor.advisor

• Rupenthal, I
• Svirskis, D
• Seyfoddin, A

Statement 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.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/33210

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/33210