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Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery.

Wang Y, Li X, Wang L, Xu Y, Cheng X, Wei P - Int J Nanomedicine (2011)

Bottom Line: The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection.In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)(0-∞) (20.343 ± 9.119 μg · h · mL(-1) vs 5.196 ± 1.426 μg · h · mL(-1)), greater clearance (2.050 ± 0.616 L · kg(-1) · h(-1) vs 0.556 ± 0.190 L · kg(-1) · h(-1)), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution.In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC(0-∞) in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Nanjing University of Technology, Nanjing, People's Republic of China.

ABSTRACT
Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)(0-∞) (20.343 ± 9.119 μg · h · mL(-1) vs 5.196 ± 1.426 μg · h · mL(-1)), greater clearance (2.050 ± 0.616 L · kg(-1) · h(-1) vs 0.556 ± 0.190 L · kg(-1) · h(-1)), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC(0-∞) in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

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The influence of homogenization pressure and cycle number on the particle size of nanosuspension.
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f3-ijn-6-1497: The influence of homogenization pressure and cycle number on the particle size of nanosuspension.

Mentions: The mean particle size and PI of paclitaxel nanosuspensions were determined by photon correlation spectroscopy to qualify the productions. The influence of homogenization pressure and cycles on the particle size and PI were shown in Figures 3 and 4. The high-pressure homogenization with increased cycle numbers resulted in the formation of smaller paclitaxel particles and PI. The particle size and PI further decreased during 6–20 cycles. However, experiments with homogenization cycles increased 25 from 20 failed to provide further decrease in particle size, which elucidated that the suspensions could not become smaller but could become more uniform during these cycles. To avoid blockage of homogenizer gap and chamber, the paclitaxel coarse powder was homogenized at 300, 500, and 800 bar pressure for six cycles respectively for pre-milling. The homogenization pressure was then increased to 1000 bar for 20 cycles until an equilibrium size was reached.


Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery.

Wang Y, Li X, Wang L, Xu Y, Cheng X, Wei P - Int J Nanomedicine (2011)

The influence of homogenization pressure and cycle number on the particle size of nanosuspension.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3141875&req=5

f3-ijn-6-1497: The influence of homogenization pressure and cycle number on the particle size of nanosuspension.
Mentions: The mean particle size and PI of paclitaxel nanosuspensions were determined by photon correlation spectroscopy to qualify the productions. The influence of homogenization pressure and cycles on the particle size and PI were shown in Figures 3 and 4. The high-pressure homogenization with increased cycle numbers resulted in the formation of smaller paclitaxel particles and PI. The particle size and PI further decreased during 6–20 cycles. However, experiments with homogenization cycles increased 25 from 20 failed to provide further decrease in particle size, which elucidated that the suspensions could not become smaller but could become more uniform during these cycles. To avoid blockage of homogenizer gap and chamber, the paclitaxel coarse powder was homogenized at 300, 500, and 800 bar pressure for six cycles respectively for pre-milling. The homogenization pressure was then increased to 1000 bar for 20 cycles until an equilibrium size was reached.

Bottom Line: The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection.In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)(0-∞) (20.343 ± 9.119 μg · h · mL(-1) vs 5.196 ± 1.426 μg · h · mL(-1)), greater clearance (2.050 ± 0.616 L · kg(-1) · h(-1) vs 0.556 ± 0.190 L · kg(-1) · h(-1)), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution.In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC(0-∞) in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Nanjing University of Technology, Nanjing, People's Republic of China.

ABSTRACT
Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)(0-∞) (20.343 ± 9.119 μg · h · mL(-1) vs 5.196 ± 1.426 μg · h · mL(-1)), greater clearance (2.050 ± 0.616 L · kg(-1) · h(-1) vs 0.556 ± 0.190 L · kg(-1) · h(-1)), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC(0-∞) in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

Show MeSH
Related in: MedlinePlus