title: Cytotoxicity considerations and electrically tunable release of dexamethasone from polypyrrole for the treatment of back-of-the-eye conditions.
abstract: Age-related macular degeneration (AMD) and diabetic macular edema (DME) are common causes of blindness in people aged over 55 years. Current treatment involves frequent intravitreal administration of corticosteroids such as dexamethasone. The aim of this research was to formulate an electrically controlled delivery system for dexamethasone. Polypyrrole (PPy) was polymerized with dexamethasone sodium phosphate (Dex-P) through two approaches. Firstly, conventional films (CFs) of PPy were electropolymerized by applying a constant current density of 2 mA/cm2for 4 min. Secondly, for the first time, we report drug-loaded ethanol-washed films (EWFs). EWFs were prepared in the same manner as CFs, except ethanol washing steps were introduced in the middle and at the end of PPy electropolymerization. The ethanol washing removed unbound PPy oligomers resulting in the formation of smooth surfaces with two distinct layers when viewed in cross-section. The EWFs showed superior electrochemical activity compared to CFs. Sustained release was observed from both CFs and EWFs with bursts of release triggered by electrical stimulation. The EWFs were initially more responsive to the electrical trigger, offering future opportunities to fine tune release. The cytotoxicity of aqueous extracts collected from both films was evaluated on human adult retinal pigment epithelium (ARPE-19) cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with negligible toxicity observed. The results suggest PPy-Dex-P films are highly suitable for the development of electro-responsive implants for the treatment of AMD and DME.
authors.affiliation: School of Pharmacy, The University of Auckland, Auckland, New Zealand.|Department of Chemistry and Biology, University of Applied Sciences Fresenius, Idstein, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ramtin
authors.affiliation: School of Pharmacy, The University of Auckland, Auckland, New Zealand.|School of Applied Sciences, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Seyfoddin
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: F P
authors.initials: FP
authors.lastname: Coutinho
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.|The MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New Zealand.
authors.forename: G I N
authors.initials: GI
authors.lastname: Waterhouse
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Auckland, New Zealand.
authors.forename: I D
authors.initials: ID
authors.lastname: Rupenthal
authors.affiliation: School of Pharmacy, The University of Auckland, Auckland, New Zealand. d.svirskis@auckland.ac.nz.
authors.forename: D
authors.identifier: 0000-0001-9435-1773
authors.initials: D
authors.lastname: Svirskis
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004563:Electrochemistry; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy; D008269:Macular Edema / Q000188:drug therapy; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D011758:Pyrroles / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D011758:Pyrroles; C067635:polypyrrole; D003907:Dexamethasone
keywords: Conducting polymer; Electrically triggered release; Ocular implant; Sequential polymerization; Smart materials; Solvent washing