Purpose: To develop an implantable device giving sustained release of ganciclovir (GCV) over 1.5 years. Methods. Short rod like pellets of GCV were prepared by compressing 30 mg of GCV in a 2 mm tablet die. Pellets were then coated in a solution of 98% hydrolyzed polyvinyl alcohol (PVA). This polymer dries to give a tough, non-erodible yet permeable coating. The pellets were then partially coated in films of the impermeable polymer ethylene vinyl acetate leaving a diffusion "port" to allow release. The assembly was then coated in PVA and heat treated to further control the release rate. Release rates were determined by immersing pellets in 5 ml of phosphate buffer (pH 7.4) and periodically sampling. Release studies were continued for up to 60 days with replacement of the receptor solution every 5-6 days. Analysis was by HPLC. Concurrent with the release work, an investigation of optimal position of suture strut was performed using human cadaver eyes. Results: Release rate was found to be primarily a function of the size of the diffusion port and alterations in the heat treatment or the use of PVA as a binder in the initial tableting step could provide further "fine" control (a factor of 2-4). Optimization allowed devices to be prepared releasing GCV at 1-2 ug/hr over the 60 day testing period. These devices have a theoretical duration of over 600 days. Work with cadaver eyes indicated that the rod style of device can be expected to be readily im plan table in human eyes. Conclusion: Implantable devices releasing GCV at 1-2 ug/hr have previously been found to effectively control CMV retinitis in man with progression occurring in newly diagnosed patients only after device depletion (1). Because of the increasing lifespan of patients with AIDS, the 600 day implant described here may represent an advantage over existing systems.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience