Abstract:
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.