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

Abstract

This study describes the pharmacokinetic behaviours 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 microns. 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 AUCfinite 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 AUCfinite 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 micrograms/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.

Pharmaceutical Applications of Plasticized Polymers

“…The plasticizer did not influence the course of degradation of polymers. Release of paclitaxel took place by the mechanism of diffusion from minimatrices (Sato et al, 1996). Analogous conclusions were published in a similar case of microspheres with etoposide (Schaefer & Singh, 2000).…”

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part II. Effect of process variables on protein model drug encapsulation efficiency

“…2007). This is the reason why the encapsulation efficiency of nanospheres is usually lower than that of microspheres Sato et al 1996). The lower encapsulation efficiencies obtained with the smaller particles was explained by the larger surface area of smaller droplets.…”

Effect of Particle Size of Nanospheres and Microspheres on the Cellular-Association and Cytotoxicity of Paclitaxel in 4T1 Cells

“…However, Cremophor EL is biologically and pharmaceutically active, causing anaphylactic hypersensitivity, hyperlipidemia, neurotoxicity, and in vitro cytotoxicity due to the formation of free radicals (9,10). In attempts to overcome the low aqueous solubility of paclitaxel as well as the undesirable toxicity of Cremophor EL, numerous alternate dosage forms have been investigated including gels (11), films (12), emulsions (13)(14)(15), liposomes (16)(17)(18), macromolecule conjugates (19), and particulate delivery systems (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

“…Nanospheres and microspheres containing paclitaxel have been investigated using various polymers such as polylactic-co-glycolic acid (PLGA) (21,(30)(31)(32)(33), poly-lactic acid (24,25), poly-ethylene oxide (25,26,31), poly-propylene oxide (27), and poly(-caprolactone) (20). The proposed advantages of particulate delivery systems for paclitaxel are that they 1) may avoid the use of toxic polyethoxylated castor oil, 2) may evade cellular efflux pumps, 3) can be administered orally or systemically, 4) inhibit tumor growth as well as prevent relapse after surgery, and 5) sustain the release of paclitaxel at therapeutic concentrations.…”

“…Hence, a faster and more complete release of paclitaxel is essential. To accelerate the release of paclitaxel, surfactants such as polyvinyl alcohol, vitamin E, and dipalmitoyl phosphatidylcholine have been added to reduce the surface tension and solubilize the hydrophobic drug (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(32)(33)(34)(35). Although, there has been significant progress in the development of particulate delivery systems containing paclitaxel, the effect of particle size of the nanospheres and microspheres preparation on the extent and mechanism of cell-association and cytotoxicity into the cancer cells has not been thoroughly investigated.…”