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This study describes an orthogonal experimental design to optimize the formulation of cisplatin (CDDP)-loaded chitosan microspheres (namely, CDDP-DAC-MS) which were produced by an emulsion-chemical cross-linking technique. Seven factors and three levels for each factor that might affect the formulation of microspheres were selected and arranged in an L27(3(13)) orthogonal experimental table. A desirability function (df) calculated according to the trapping efficiency of CDDP, the drug content (%, w/w), and the size distribution of each batch of microspheres was introduced as an index of the microsphere formulation. The overall desirability functions (DF) were produced and treated by a statistic analytical system to optimize the formulation. Moreover, the contour maps were produced to analyze the influence of the seven factors on the size distribution, the drug content, and the drug trapping efficiency. The established optimum procedure was reproducible. Scanning electron micrographs showed that CDDP-DAC-MS were spherical with a coarse surface. The average diameter, drug content, and drug trapping efficiency of CDDP-DAC-MS were 74.8 microns, 20.8% (w/w), and 77.5%, respectively. The in vitro release of cisplatin from chitosan microspheres in saline was retarded compared with that from saline solution; the release of CDDP from chitosan microspheres was suggested to be controlled by the dissolution and diffusion of the drug from the chitosan matrix.

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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.

This paper investigates the trajectory design issue for the transfer from the Lissajous orbit of CHANGE 2 probe to asteroids. First, an intersection search method, which is a general design method of low-energy transfer trajectories by searching the intersection of unstable and stable manifolds in the circular restricted three-body problem (CRTBP), is applied to produce the zero-cost flyby trajectories for the asteroid flyby missions of CHANGE 2 probe, and the simulation result shows that this method is invalid. Then, for this trajectories design issue, a perturbation method, which consists of a process of searching initial trajectories by applying velocity perturbations in the direction of unstable eigenvectors of the Lissajous orbit and a trajectory correction process with two-level differential correction, is proposed. Finally, the transfer opportunities between the Lissajous orbit of CHANGE 2 and asteroids Toutatis and 2010 JK1 are searched by the perturbation method. The results show that the method proposed in this paper can identify low-energy transfer trajectories for asteroid flyby missions of CHANGE 2. Moreover, this method provides a global understanding of the trend of impulsive maneuvers over the transfer date.