Characterization, pharmacokinetics and disposition of novel nanoscale preparations of paclitaxel

Polymeric nanoparticles (NPs) have great potential application in achieving targeted delivery of anticancer drugs. Paclitaxel (PTX) loaded NPs were developed using biodegradable methoxy poly (ethylene glycol)–poly (ɛ-caprolactone) (MPEG–PCL) diblock copolymer by solid dispersion technique without toxic organic solvent. The lyophilized powder has been stored at room temperature for more than six months and still unchanged. PTX-loaded MPEG–PCL nanoparticles (PTX-NPs) displayed that the highest drug loading of PTX was about 25.6% and entrapment efficiency was over 98%, and the optimized average diameter and polydispersity index (PDI) were about 27.6 ± 0.1 nm and 0.05, respectively. Moreover, experimental results shown PTX-NPs had sustained-release effects and its curve fitting followed the Higuchi model. The maximum tolerated dose (MTD) of PTX-NPs after single dose in Balb/c mice was above 80 mg PTX/kg body weight (b.w), which was 2.6-fold higher than that of Taxol® (30 mg PTX/kg b.w). The levels of PTX administrated PTX-NPs had obvious distinction to Taxol® in plasma, liver, spleen, kidneys, lungs, heart and tumor. Especially, the concentration of PTX in tumor administrated PTX-NPs was higher than administration of Taxol®. All results suggested that we had contrived a simple, biodegradable, effective and controllable drug delivery system for paclitaxel.

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