Abstract
A viscous bioerodible and hydrophobic poly(ortho ester) has been developed as a biocompatible, sustained drug release system for an ophthalmic application in intraocular proliferative disorders. The combination of wound healing modulators such as 5-fluorouracil and dexamethasone is a major advantage since these drugs act at different stages of these diseases. Since 5-fluorouracil is an acidic, water-soluble compound and dexamethasone exists in three chemical forms, i.e. the water-insoluble base, the highly hydrophobic acetate ester or the basic phosphate salt, it was of interest to investigate whether the physicochemical properties of the drugs have an influence on their release rates, and whether a concomitant and sustained release of both 5-fluorouracil and dexamethasone could be achieved. It has been found that lipophilicity and acidobasicity play a major role in controlling drug release rates and polymer degradation. The combination of 5-fluorouracil and dexamethasone phosphate allows a sustained and concomitant release of both drugs, due to the basic characteristics of the corticosteroid which stabilize the polymer. This system appears to be promising for concomitant and controlled drug delivery aimed at the pharmacological treatment of intraocular proliferative disorders.
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