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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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Related in: MedlinePlus

The influence of different ratios of poloxamer 188 and PEG-400 on the particle size.Abbreviation: PEG-400, polyethylene glycol 400.
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f1-ijn-6-1497: The influence of different ratios of poloxamer 188 and PEG-400 on the particle size.Abbreviation: PEG-400, polyethylene glycol 400.

Mentions: The influence of the proportion of poloxamer 188 and PEG-400 was investigated at the same experiment condition when the concentrations of paclitaxel and surfactant were fixed (0.04% and 0.08%, w/v). As shown in Figure 1, the proportion extent 1:1–1:2 was suitable.


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 different ratios of poloxamer 188 and PEG-400 on the particle size.Abbreviation: PEG-400, polyethylene glycol 400.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-6-1497: The influence of different ratios of poloxamer 188 and PEG-400 on the particle size.Abbreviation: PEG-400, polyethylene glycol 400.
Mentions: The influence of the proportion of poloxamer 188 and PEG-400 was investigated at the same experiment condition when the concentrations of paclitaxel and surfactant were fixed (0.04% and 0.08%, w/v). As shown in Figure 1, the proportion extent 1:1–1:2 was suitable.

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