IN-VITRO AND IN-VIVO EVALUATION OF PLAGA-(50 50) MICROSPHERES CONTAINING 5-FLUOROURACIL PREPARED BY A SOLVENT EVAPORATION METHOD/

Poly (DL-lactide-co-glycolide) PLAGA (50/50) microspheres containing a n antineoplastic drug, 5-fluorouracil (5-FU) were prepared by a solven t evaporation process in order to passively target liver carcinomas. T he microspheres were spherical with diameters 2-5 mu m and encapsulate d more than 70% (w/w) of the 5-FU. In vitro release patterns of 5-FU f rom microspheres were determined for various systems. It was found tha t drug release depended upon the amount of entrapped drug, the polymer molecular weight and pH of the dissolution medium. The in vitro relea se mechanism was diffusion controlled and followed a square-root of ti me relationship. In vivo distribution of Tc-99m labeled microspheres a fter intravenous injection into mice was characterized by an initially high uptake by organs of the mononuclear phagocyte system (MPS). Foll owing i.v. administration of fluorescein-labeled PLAGA microspheres, a ccumulation was into the MPS, mainly the Kupffer cells cytoplasm and n ear the liver sinusoids.