5-FU LOADED PHEMA DRAINAGE IMPLANTS FOR GLAUCOMA-FILTERING SURGERY - DEVICE DESIGN AND IN-VITRO RELEASE KINETICS

Implantable monolithic and reservoir-like water-swellable drainage dev ices were developed for the subconjunctival sustained release of 5-flu orouracil (5-FU) in glaucoma-filtering surgery. A water-swellable matr ix was formed of a copolymer of 2-hydroxyethyl methacrylate (HEMA) wit h different amounts of ethylene glycol dimethacrylate (EGDMA). Drug in corporation was done before polymerization and cross-linking. Briefly, to prepare the monolithic device the monomer-drug mixture is compress ion moulded into a 10 mm cylinder of 1 mm length. Furthermore, reservo ir-like devices were obtained by coating the monolithic devices with a highly cross-linked polymer of HEMA (pHEMA) composition. The pHEMA de vices containing 5-FU or not were well characterized by means of dynam ic swelling studies, structural and thermal analysis. The release of 5 -FU from these implants was studied in vitro. The rate of drug release was controlled by changing the drug loading (i.e. 10 mg or 20 mg 5-FU per device), cross-linking density of polymer matrix and type of impl antable device, i.e. monolithic or reservoir-like device. While monoli thic devices are releasing total releasable 5-FU during the first 10 h , reservoir-like devices prolong 5-FU release for up to 120 h. The 5-F U diffusion coefficient in swollen devices (D-s,D-s) is in the order o f 10(-8) cm(2) s(-1) (approximately 10 times smaller than D-w,D-g valu es) and it is dependent on the cross-linking density of polymeric matr ix and device load. These preliminary results suggested that 20 mg 5-F U-loaded reservoir-like devices may be a potentially effective system to deliver 5-FU into the subconjunctiva.