Pharmacokinetic Study of Taxol-Loaded Poly(lactic-co-glycolic acid) Microspheres Containing Isopropyl Myristate after Targeted Delivery to the Lung in Mice

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This study describes the pharmacokinetic behaviors of taxol after intravenous administration of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate (namely, Taxol-IPM-PLGA-MS) and taxol saline solution to mice. Taxol-IPM-PLGA-MS were prepared using a solvent evaporation technique. The drug content and trapping efficiency of taxol in the microspheres were 5.09% (w/w) and 98%, respectively; the average diameter of the microspheres was 30.1 μm. Scanning electron microscopy showed that Taxol-IPM-PLGA-MS were spherical with 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 plasma but relatively lower than those in kidneys, bile, and liver. The biodistribution of taxol after administration of Taxol-IPM-PLGA-MS (3 mg taxol/kg), on the other hand, was altered significantly from the control (taxol solution) group. No taxol was detected in plasma or bile within 3 weeks, and only very low level of taxol was detected in the kidneys or liver within 48 h. However, taxol concentrations in the lung were increased significantly with the microsphere group; the peak concentration of taxol and AUC_<finite> in the lung was three times and 500 times higher than those with the taxol solution group, respectively.It was also noticed that the taxol levels in the lung were maintained at relatively high levels (>10 μg/ml) for 3 weeks. Thus, the present study demonstrated the effective targeted delivery of taxol to the lung of mice using Taxol-IPM-PLGA-MS.
公益社団法人日本薬学会の論文
1996-12-15

Pharmacokinetic Study of Taxol-Loaded Poly(lactic-co-glycolic acid) Microspheres Containing Isopropyl Myristate after Targeted Delivery to the Lung in Mice

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