Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery.
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.
['Wang|Yonglu|Y|', 'Li|Xueming|X|', 'Wang|Liyao|L|', 'Xu|Yuanlong|Y|', 'Cheng|Xiaodan|X|', 'Wei|Ping|P|']
D000818:Animals D019540:Area Under Curve D002152:Calorimetry, Differential Scanning D004337:Drug Carriers D004355:Drug Stability D005260:Female D005612:Freeze Drying D006207:Half-Life D007275:Injections, Intravenous D008297:Male D051379:Mice D008813:Mice, Inbred ICR D046529:Microscopy, Electron, Transmission D053758:Nanoparticles D017239:Paclitaxel D010316:Particle Size D011312:Pressure D051381:Rats D017207:Rats, Sprague-Dawley D013501:Surface-Active Agents D013535:Suspensions D014018:Tissue Distribution
high-pressure homogenization tissue distribution surfactant