BIOCOMPATIBILITY OF A NEW SEMISOLID BIOERODIBLE POLY(ORTHO ESTER) INTENDED FOR THE OCULAR DELIVERY OF 5-FLUOROURACIL

The biocompatibility of a new semisolid, hydrophobic poly(ortho ester) (POE) intended for controlled drug delivery to the eye was evaluated. The polymer was injected subconjunctivally in rabbits, and clinical a nd histologic examinations were performed 3, 10, 15, and 21 days after injection. Polymers injected as controls were an aqueous gel of sodiu m hyaluronate (SH), 1% in phosphate buffer, and medical grade silicone oil. After injection, the POE emulsified into small droplets and a fo cal eosinophilic reaction was noted at 3 days' implantation. At 10 day s' implantation, the POE was not identified in the implantation site a nd the inflammatory reaction had resolved, with fibroblasts being the predominant cell type. At 15 and 21 days, no POE was identified and no rmal appearing tissue was present in the injection site. Sodium hyalur onate was not inflammatory over the period of the implantations. Silic one ail induced a slight inflammation at 3 days, with the presence of eosinophils and limited necrosis with cellular debris. Silicone oil wa s present in the implantation site at 3, 10, 15, and 21 days. The infl ammatory response to the respective polymers was evaluated in the subc onjunctival tissue. The inflammatory reaction was quantified at the im plant site, adjacent subconjunctival tissues, and scleral and corneal stroma. The inflammatory cell densities in these respective tissue zon es were determined, and the ratio of eosinophils over total inflammato ry cells was calculated. POE did not become encapsulated with fibrous tissue, but biodegraded in a short time, indicating its potential for use after glaucoma filtration surgery. (C) 1994 John Wiley and Sons, I nc.