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Angela Glendenning, Karen Crews, Jill Sturdivant, Mitchell A deLong, Casey Kopczynski, Cheng-Wen Lin; Sustained Release, Biodegradable PEA Implants for Intravitreal Delivery of the ROCK/PKC Inhibitor AR-13503. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5672.
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Aerie has developed a library of kinase inhibitors for the treatment of ocular and other diseases. AR-13503 is a potent Rho kinase (ROCK) and protein kinase C (PKC) inhibitor under development for the treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). Its physicochemical and pharmacological properties are well suited for posterior segment diseases. The purpose of this work was to identify a compatible sustained release technology that provides a 4 to 6 month duration of drug release following intravitreal injection.
AR-13503 was incorporated with various biodegradable poly-lactic-co-glycolic acid (PLGA) and polyester amide (PEA) polymers. PLGA/AR-13503 implants were manufactured by PRINT® technology. PEA/AR-13503 implants were manufactured by solvent casting and injection molding. Both PLGA/AR-13503 and PEA/AR-13503 implants were manufactured to dimensions compatible with injection through a 27-gauge needle. In vitro drug release and chemical stabilities were assessed at pH 7.4 at 37°C and analyzed by HPLC.
PLGA polymers were chemically incompatible with AR-13503, whereas the PEA polymer showed excellent compatibility with AR-13503. PEA polymer implants containing AR-13503 provided a zero-order sustained drug release with minimal initial burst on Day 1 (<2%). Linear drug release was sustained in vitro for over 100 days.
Aerie developed a biodegradable implant for AR-13503 using a novel PEA polymer that provides sustained drug release for more than 100 days. These results support further development of the AR-13503 PEA implant for the treatment of DME and nAMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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