title: 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-β-cyclodextrin or β-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.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, University of Navarra, Pamplona, 31008, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Calleja
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, University of Navarra, Pamplona, 31008, Spain.
authors.forename: Socorro
authors.initials: S
authors.lastname: Espuelas
authors.affiliation: Physicochimie, Pharmacotechnie, Biopharmacie, UMR 8612, Université Paris-Sud XI, Châtenay-Malabry, 92296, France.|CNRS, Chatenay-Malabry, F-92296, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Vauthier
authors.affiliation: Physicochimie, Pharmacotechnie, Biopharmacie, UMR 8612, Université Paris-Sud XI, Châtenay-Malabry, 92296, France.|CNRS, Chatenay-Malabry, F-92296, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponchel
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, University of Navarra, Pamplona, 31008, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Irache
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007408:Intestinal Absorption; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
chemical_list: D000812:Anhydrides; D000972:Antineoplastic Agents, Phytogenic; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: bioavailability; controlled release; cyclodextrins; nanoparticles; paclitaxel; pegylation; permeability; transmucosal delivery