PHARMACOKINETIC STUDY OF TAXOL-LOADED POLY(LACTIC-CO-GLYCOLIC ACID) MICROSPHERES CONTAINING ISOPROPYL MYRISTATE AFTER TARGETED DELIVERY TO THE LUNG IN MICE

This study describes the pharmacokinetic behaviors of taxol after intr avenous administration of taxol-loaded poly(lactic-co-glycolic acid) m icrospheres containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline solution to mice. Taxol-IPM-PLGA-MS were prepared us ing a soh ent evaporation technique, The drug content and trapping eff iciency of taxol in the microspheres were 5.09% (w/w) and 98%, respect ively; the average diameter of the microspheres was 30.1 mu m, Scannin g electron microscopy showed that Taxol-IPM-PLGA-MS were spherical wit h a smooth surface. After administration of the drug saline solution ( 3 mg taxol/kg), taxol disappeared rapidly from plasma within 4-6 h and distributed extensively in various tissues. The tissue levels and AUC (finite) of taxol in the lung were obviously higher than those in plas ma hut relatively lo,rer than these in kidneys, bile, and liver. The b iodistribution of taxol after administration of Taxol-IPM-PLGA-MS (3 m g taxol/kg), on the other hand, was altered significantly from the con trol (taxol solution) group, No taxol was detected in plasma or bile w ithin 3 weeks, and only very low level of taxol was detected in the ki dneys or liver within 48 h, However, taxol concentrations in the lung were increased significantly with the microsphere group; the peak conc entration of taxol and AUC(finite) in the lung was three times and 500 times higher than these with the taxol solution group, respectively, It was also noticed that the taxol levels in the lung were maintained at relatively high levels (>10 mu g/ml) for 3 weeks, Thus, the present study demonstrated the effective targeted delivery of taxol to the lu ng of mice using Taxol-IPM-PLGA-MS.