Ocular delivery using poly(ortho esters)

Three families of poly(ortho esters) were investigated as a means of delivering 5-fluorouracil (5-FU), an antiproliferative agent used as an adjunct to glaucoma filtering surgery. Release of 5-FU from a crosslinked POE II occurred predominantly by diffusion with little weight loss, while release of 5-FU from a linear polymer occurred by an erosion-controlled process confined predominantly to the surface layers. No ocular biocompatibility studies were carried out. Rate of release of 5-FU from POE III, a viscous, injectable material, could be controlled by polymer molecular weight and polymer hydrophobicity. Excellent biocompatibility was demonstrated in subconjunctival, intravitreal and suprachoroidal injections. Polymer lifetime in the various sites investigated was between 1 and 3 weeks. The effect of sustained 5-FU release was investigated in rabbits that underwent a trabeculectomy and the effectiveness of maintaining low intraocular pressure for 1 month demonstrated. Release of 5-FU from POE IV was investigated using both solid and viscous, injectable materials. Good control over rate of 5-FU release by an erosion-controlled process was achieved from both types of formulations. Excellent biocompatibility was demonstrated in subconjunctival, intracameral, intravitreal and suprachoroidal injections. Lifetimes in the various sites ranged from 5 weeks for subconjunctival injections to 3 months for intravitreal injections to more than 6 months for intracameral and suprachoroidal injections.