Novel farnesylthiosalicylate (FTS)-eluting composite structures.

Farnesylthiosalicylate (FTS) is a new specific nontoxic drug with a mild hydrophobic nature, which acts as a Ras antagonist and can therefore be used for stent applications as well as for local cancer treatment. FTS-loaded bioresorbable core/shell fiber structures were developed and studied in order to investigate the FTS release mechanism. These structures were composed of a polyglyconate core and a porous poly(d,l-lactic-glycolic acid) shell loaded with FTS, prepared using freeze drying of inverted emulsions. The effects of the emulsion's composition (formulation) and process kinetics on the FTS release from the coatings were studied with reference to the shell morphology and degradation profile. The FTS release profiles exhibited a burst effect accompanied by a release rate which decreased with time and lasted for 15-40 days. The process was found to affect the drug release profile via two routes: (1) Direct, through water uptake and swelling of the structure, leading to a FTS burst release. Degradation of the host polymer affects the FTS release rate at a later stage. (2) Indirect effect of the microstructure on the release profile, which occurs via an emulsion stability mechanism. The copolymer composition is the most important parameter affecting the release behavior in our system. Other parameters, including polymer content, O:A phase ratio and homogenization rate exhibited only minor effects on the FTS release profile. The controlled release of the new drug FTS is reported here for the first time.