MICROSPHERES OF 5-FLUOROURACIL USING POLY(DL-LACTIC ACID) - IN-VITRO RELEASE PROPERTIES AND DISTRIBUTION IN MICE AFTER IV ADMINISTRATION

Microspheres of 5-fluorouracil have been prepared from poly(dl-lactic acid) (PLA) utilizing a solvent evaporation technique under ambient conditions. Polymers of three different molecular weights were used. The release kinetics of poly(dl-lactic acid) microspheres were studied in buffer solutions (of pH 1.2, 7.4 and 9.6) and saline solution at 37-degrees-C. A correlation was established between solubility of 5-fluorouracil in these buffer solutions and release rate which is also linearly related to the molecular weight of the polymers. After intravenous injection of Tc-99m-labeled 5FU microspheres into mice, PLA2 (MW: 109 000 Da) and PLA3 (MW: 33 300 Da) formulations accumulated predominantly in the liver. The histologic study showed that PLA1 (MW: 118 300 Da) microspheres accumulated in the lung tissue till 4 h but PLA2 and PLA3 microspheres accumulated in the liver at the same time.