Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma
Purpose We developed polycaprolactone (PCL) implants that achieve zero order release of a proprietary ocular hypotensive agent (DE 117) over 6 months. Methods The release rates of DE 117 loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE 117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS) Results In vitro release of DE 117 showed zero order release with a release rate of 0.5 mg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE 117 and hDE 117 (the hydrolyzed active form of DE 117) in ocular tissues (cornea, iris ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE 117 and its conversion to hDE 117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE 117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device. Conclusions Proof of concept PCL drug delivery devices containing DE 117 show promise as a long term glaucoma treatment based on their zero order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues.
Investigative ophthalmology visual science