Combined hydroxypropyl-beta-cyclodextrin and poly(anhydride) nanoparticles improve the oral permeability of paclitaxel.
The aim of this work was to study the effect of the combination between 2-hydroxypropyl-beta-cyclodextrin (HPCD) and bioadhesive nanoparticles on the encapsulation and intestinal permeability of paclitaxel (PTX). In this context, a solid inclusion complex between PTX and HPCD was prepared by an evaporation method. Then, the complex was incorporated in poly(anhydride) nanoparticles by a solvent displacement method. The resulting nanoparticles, PTX-HPCD NP, displayed a size of about 300 nm and a drug loading of about 170 microg/mg (500-fold higher than in the absence of HPCD). The effect of these nanoparticles on the permeability of intestinal epithelium was investigated using the Ussing chamber technique. The apparent permeability (P(app)) of PTX was found to be 12-fold higher when formulated as PTX-HPCD NP than when formulated as Taxol (control). Furthermore, when interaction between nanoparticles and the mucosa was avoided, the permeability of PTX significantly decreased. In summary, the association between PTX-HPCD and poly(anhydride) nanoparticles would induce a positive effect over the intestinal permeability of paclitaxel, being the bioadhesion a mandatory condition in this phenomena.
Agüeros
M
M
Department of Pharmacy, University of Navarra, 31008 Pamplona, Spain.
Ruiz-Gatón
L
L
Vauthier
C
C
Bouchemal
K
K
Espuelas
S
S
Ponchel
G
G
Irache
J M
JM
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D004338:Drug Combinations; D004357:Drug Synergism; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D049388:Polyanhydrides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004338:Drug Combinations; D049388:Polyanhydrides; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017239:Paclitaxel