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 an antineoplastic drug, 5-fluorouracil (5-FU) were prepared by a solvent evaporation process in order to passively target liver carcinomas. The microspheres were spherical with diameters 2-5 mu m and encapsulated more than 70% (w/w) of the 5-FU. In vitro release patterns of 5-FU from microspheres were determined for various systems. It was found that drug release depended upon the amount of entrapped drug, the polymer molecular weight and pH of the dissolution medium. The in vitro release mechanism was diffusion controlled and followed a square-root of time relationship. In vivo distribution of Tc-99m labeled microspheres after intravenous injection into mice was characterized by an initially high uptake by organs of the mononuclear phagocyte system (MPS). Following i.v. administration of fluorescein-labeled PLAGA microspheres, accumulation was into the MPS, mainly the Kupffer cells cytoplasm and near the liver sinusoids.