Intestinal permeation enhancement of docetaxel encapsulated into methyl-β-cyclodextrin/poly(isobutylcyanoacrylate) nanoparticles coated with thiolated chitosan.
In this study we investigated the potential of mucoadhesive nanoparticles to enhance the intestinal permeability of docetaxel (Dtx). These nanoparticles were composed of methyl-β-cyclodextrin (Me-β-CD) combined with poly(isobutylcyanoacrylate) and coated with thiolated chitosan. In order to encapsulate the highest amount of Dtx into nanoparticles, the anionic emulsion polymerization of isobutylcyanoacrylate was carried out in a solution of Me-β-CD/Dtx inclusion complex. The resulting nanoparticles were spherical with diameters ranging from 200 to 400 nm, and positively charged. Depending on the formulation, the encapsulation efficiency of Dtx was 70-80%. In vitro experiments in simulated intestinal medium containing 1% w/v of pancreatin showed that Dtx was gradually released to reach 60% after 24h and 100% after 48 h. The capacity of these nanoparticles to enhance the flux of Dtx across the intestinal membrane was then investigated using the Ussing chamber technique. The intestinal permeation of Dtx loaded into nanoparticles was found to be higher than the ethanol control solution of Dtx. Interestingly, when mucoadhesive interactions between nanoparticles and the mucosa were avoided, the intestinal permeation of Dtx significantly decreased, confirming that the mucoadhesion of the nanoparticles was a mandatory condition to enhance the intestinal permeation of Dtx.
UMR CNRS 8612, Institut Galien Paris Sud, Université Paris-Sud, School of Pharmacy, 5 Rue J.B. Clément, 92296 Châtenay Malabry Cedex, France.
Silvia
S
Mazzaferro
Kawthar
K
Bouchemal
Rym
R
Skanji
Claire
C
Gueutin
Hélène
H
Chacun
Gilles
G
Ponchel
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000737:chemistry; D000077143:Docetaxel; D004659:Enbucrilate; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010194:Pancreatin / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
D000970:Antineoplastic Agents; D003487:Cyanoacrylates; D043823:Taxoids; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000077143:Docetaxel; D010194:Pancreatin; D048271:Chitosan; D004659:Enbucrilate