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: beta-cyclodextrin (CD), 2-hydroxypropyl-beta-cyclodextrin (HPCD) and 6-monodeoxy-6-monoamino-beta-cyclodextrin (NHCD). A single dose of 10mg paclitaxel per kg body weight as PTX-cyclodextrin nanoparticles was used. Plasma curves were characterised by a plateau of paclitaxel concentration close to the C(max) from T(max) till 24h 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.
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