Biocompatibility and biodegradation of intravitreal hyaluronan implants in rabbits

To study the biocompatibility and the biodegradation rate in vivo of new intravitreal implants made with three different hyaluronic acid esters: Hyaff7, Hyaff11 and Hyaff11p75 (100% ethyl ester, 100 and 75% benzyl esters, respectively), the plugs were implanted through a sclerotomy at 3.5 mm from the limbus of rabbit eyes. In order to evaluate the in vivo biodegradation the shaft diameter of the plugs was measured by ultrasound biomicroscopy. Slit lamp microscopy, ophthalmoscopy and ERG were performed periodically. The effects of the implants on ocular tissues were also evaluated histologically. All the plugs showed a good biocompatibility. Plugs of both the total esters, Hyaff7 and Hyaff11, were found to undergo a slow dissolution process for 60 and 150 days, respectively. The partial benzyl ester, Hyaff11p75, was completely reabsorbed after 15 days. Analysis of variance showed a high correlation between biodegradation rate and the time of resorption (F = 90.5; p < 0.001). The biodegradation rate of each implant is related to the chemical structure of the three types of Hyaff (F = 4.51; p = 0.005). The present data suggest that intravitreal implants based on hyaluronic acid esters represent useful biocompatible and biodegradable devices for a potential drug delivery system in the treatment of posterior segment ocular diseases. (C) 2000 Elsevier Science Ltd. All rights reserved.