NEW-GENERATION OF POLY(ORTHO ESTERS) - SYNTHESIS, CHARACTERIZATION, KINETICS, STERILIZATION AND BIOCOMPATIBILITY

After a brief historical overview of the development of three families of poly(ortho esters) (POEs), the physico-chemical characteristics, d rug release properties and biocompatibility of the third generation is discussed. Its synthesis is based on a transesterification reaction b etween 1,2,6-hexanetriol and trimethylorthoacetate. This viscous hydro phobic polymer has been used for the sustained release of 5-fluorourac il (5-FU) or mitomycin C (MMC) in glaucoma filtering surgery. It shows a good correlation between drug release and polymer erosion and can b e injected using a hydraulic syringe. Drug release can be modulated by using different molecular weights of the polymer, or by adding basic or acidic excipients. Because conventional sterilization methods using gamma or electron beam-irradiation can not be used due to changes in molecular weight and dynamic viscosity resulting from backbone cleavag e, an aseptic fabrication procedure has been developed and validated. POE biocompatibility has been established after subconjunctival inject ions of POE, monomers and degradation products in rabbits. Better cont rol of the microenvironmental pH during polymer degradation has been a chieved by using an in situ formed buffer system. (C) 1997 Elsevier Sc ience B.V.