METHYLMETHACRYLATE SULFOPROPYLMETHACRYLATE COPOLYMER NANOPARTICLES FOR DRUG-DELIVERY - PART III - EVALUATION AS DRUG-DELIVERY SYSTEM FOR OPHTHALMIC APPLICATIONS

Copolymer nanoparticles were investigated as carrier systems for the t opical ophthalmic application of the muscarinic agonists arecaidine pr opargyl ester (APE) and (S)-(+)-aceclidine in rabbits and compared to conventional eye drop preparations. The copolymer nanoparticles were p repared by free radical polymerization of methylmethacrylate (MMA) and sulfopropylmethacrylate (SPM). The in-vivo activity of the drug-conta ining carrier systems was tested by the measurement of the miotic effe ct observed after local administration in rabbits. It has been found t hat the copolymer nanoparticles were able to produce a significant inc rease of the ocular APE bioavailability as determined by the area unde r the miosis-time-curve (AUC). The nanoparticle preparations were tole rated without any irritating effect in the rabbit eye. Besides the cop olymer nanoparticles, different formulations containing bioadhesive or viscosity-enhancing polymers with and without additional nanoparticle s were tested. The administration of APE-loaded copolymer nanoparticle s was found to be equivalent in efficacy to solutions containing the s oluble polymers without nanoparticles. The combination of the nanopart icles with bioadhesive polymers further increased the ocular drug bioa vailability. Hyaluronic acid alone or in combination with copolymer na noparticles was observed to be the most effective soluble polymer for ophthalmic application by enhancing the AUC of miosis-time-curve 2-fol d. Similar effects induced by the carrier systems were obtained with ( S)-(+)-aceclidine. However, the magnitude of the enhancement of the mi otic effect that is achievable by the binding of the drug to nanoparti cles over free drug is much more pronounced with the short acting drug APE than with (S)-(+)-aceclidine. (C) 1997 Elsevier Science B.V.