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J. Kohn, J. Khan, C. Iovine, P. Velagaleti; Development of a Bioerodible Insert for the Ocular Delivery of a Novel Next Generation Calcineurin Inhibitor. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5007. doi: https://doi.org/.
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The local delivery of sustained, effective concentrations of immunosuppressive therapy that is safe, well-tolerated, and suitable for long-term use is a major need within the ophthalmic disease treatment community.
The development of a small, implantable bioerodible drug delivery device appropriate for the treatment of various immune-based ophthalmic conditions is presented here. The new device is a composite matrix consisting of a resorbable thermoplastic terpolymer and a novel cyclic peptide calcineurin inhibitor (LX211/ISA247). LX211 (ISA247), as an oral formulation, is currently in Phase III development for the treatment of non-infectious, idiopathic uveitis.
In order to optimize the delivery system of this implantable device, various candidate matrix polymers were selected from a large, combinatorial library of bioerodible polyarylates and polycarbonates, based on desaminotyrosyltyrosine alkyl ester as the main dipeptide monomer component of the polymer chain. The suitability of the various polyarylate and polycarbonate compositions in this drug-eluting device was further characterized using the following measures: drug release kinetics, polymer molecular weight degradation, polymer mass loss by erosion, and water uptake. The overall device design parameters necessary for producing bioerodible ocular implants are presented here. Thus, an optimal sustained yet tunable drug release profile for a novel implantable ocular device was obtained by molecular engineering of the chemical composition and physical properties of the matrix polymer.
The development of a bioerodible implant for the ocular delivery of a novel, next generation calcineurin inhibitor represents a new, hybrid mechanism of drug release that is capable of sustained peptide release from 6 to 24 months and has potential clinical implications for the treatment of immune-based ophthalmic conditions.
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