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

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-mono-deoxy-6-monoamino-beta-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 C(max) from T(max) till 24 is 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. (C) 2010 Elsevier B.V. All rights reserved.