Controlled Release, Intestinal Transport, and Oral Bioavailablity of Paclitaxel Can be Considerably Increased Using Suitably Tailored Pegylated Poly(Anhydride) Nanoparticles.

ABSTRACT

The aim of the work was to evaluate in vitro and in vivo the effect of the addition of poly(ethylene glycol) (PEG) to paclitaxel (PTX)-cyclodextrin poly(anhydride) nanoparticles. For this, PTX in poly(anhydride) nanoparticles complexed with cyclodextrins (either 2-hydroxypropyl-ß-cyclodextrin or ß-cyclodextrin) and combined with PEG 2000 were prepared by the solvent displacement method. Intestinal permeability in vitro and in vivo pharmacokinetic studies in C57BL/6J mice were performed. Nanoparticle formulations containing PTX increased its apparent permeability through rat intestine in vitro in the Ussing chambers, enhancing its permeability 10-15 times compared with commercial Taxol®. In addition, in pharmacokinetic studies, drug plasma levels were observed for at least 24 h leading to a relative oral bioavailability between 60% and 80% for PTX complexed with cyclodextrin and loaded in pegylated poly(anhydride) nanoparticles after oral gavage. In all, PTX-cyclodextrin complexes encapsulated in pegylated nanoparticles managed to promote the intestinal uptake of the drug displaying sustained plasma levels after oral administration to laboratory animals with a more prolonged plasma profile compared with the formulation with no PEG at all. Therefore, pegylated poly(anhydride) nanoparticles represent a promising carrier for the oral delivery of PTX.