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Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles

2010; Elsevier BV; Volume: 145; Issue: 1 Linguagem: Inglês

10.1016/j.jconrel.2010.03.012

1873-4995

Maite Agüeros, Virginia Zabaleta, Socorro Espuelas, M. A. Campanero, Juan M. Irache,

HER2/EGFR in Cancer Research

The aim of this work was to study the oral bioavailability in rats of paclitaxel (PTX) when encapsulated as a complex with cyclodextrins in poly(anhydride) nanoparticles (NP). For this purpose three different cyclodextrins were selected: β-cyclodextrin (CD), 2-hydroxypropyl-β-cyclodextrin (HPCD) and 6-monodeoxy-6-monoamino-β-cyclodextrin (NHCD). A single dose of 10 mg paclitaxel per kg body weight as PTX–cyclodextrin nanoparticles was used. Plasma curves were characterised by a plateau of paclitaxel concentration close to the Cmax from Tmax till 24 h post-administration. For PTX–CD NP and PTX–HPCD NP, these sustained levels of the anticancer drug were found to be between 27 and 33-fold higher than the reported value of drug activity whereas the relative oral bioavailability of paclitaxel was calculated to be higher than 80%. These facts would be directly related with a synergistic effect obtained by the combination of the bioadhesive properties of poly(anhydride) nanoparticles and the inhibitory effect of cyclodextrins on the activity of P-glycoprotein and cythocrome P450.