PolyActiva is developing ocular implants that enable slow release, site specific drug delivery directly to the eye, from an implant that erodes completely. They are produced from a proprietary drug-polymer conjugate technology. Key attributes include:
· Higher drug loadings per mass of polymer than currently available.
· Controlled and selective drug release with drug pendent to the polymer backbone.
· Complete polymer bioerosion leaving no residue and producing safe by-products
· A modular nature that enables properties to be tuned to meet requirements
An intravitreal implant that delivers the antibiotic levofloxacin (LVX) for the post-surgical prophylaxis and treatment of bacterial endophthalmitis (a catastrophic inflammatory reaction to eye infection) has been developed. LVX was covalently attached to a monomer unit via a selectively labile linker and polymerised with suitable co-monomers to give a final polymer implant with the desired characteristics. Performance was assessed by analysis of in vitro release kinetics and evaluation of pharmacokinetics and efficacy in an animal model.
Results showed:
· At the high drug loadings achieved (ca. 50%) the drug’s physicochemical properties played a significant role in the polymer’s attributes, including drug release rates.
· Zero-order release of LVX over at least 30 days.
· Drug release is a function of implant mass
· In vitro release of levofloxacin (5-40 mg/day) at therapeutic levels over an extended period (up to 120 days).
· LVX concentrations in vitreous matched steady-state levels predicted from pharmacokinetic calculations based on the in vitro release rate, and were well above the MIC for S. aureus for at least a 10-day treatment period.
· Infection is cleared or prevented in a validated rabbit endophthalmitis model from administration of a single implant.
A second ocular implant programme for the delivery of an agent for the treatment of glaucoma is underway.