title: Sunitinib-eluting beads for chemoembolization: methods for in vitro evaluation of drug release.
abstract: Drug-eluting microspheres are used for embolization of hypervascular tumors and allow for local controlled drug release. Although the drug release from the microspheres relies on fast ion-exchange, so far only slow-releasing in vitro dissolution methods have been correlated to in vivo data. Three in vitro release methods are assessed in this study for their potential to predict slow in vivo release of sunitinib from chemoembolization spheres to the plasma, and fast local in vivo release obtained in an earlier study in rabbits. Release in an orbital shaker was slow (t50%=4.5h, 84% release) compared to fast release in USP 4 flow-through implant cells (t50%=1h, 100% release). Sunitinib release in saline from microspheres enclosed in dialysis inserts was prolonged and incomplete (t50%=9 days, 68% release) due to low drug diffusion through the dialysis membrane. The slow-release profile fitted best to low sunitinib plasma AUC following injection of sunitinib-eluting spheres. Although limited by lack of standardization, release in the orbital shaker fitted best to local in vivo sunitinib concentrations. Drug release in USP flow-through implant cells was too fast to correlate with local concentrations, although this method is preferred to discriminate between different sphere types.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland. Electronic address: katrin.fuchs@unige.ch.
authors.forename: Katrin
authors.initials: K
authors.lastname: Fuchs
authors.affiliation: Departments of Radiology and Interventional Radiology, CHUV Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: pierre.bize@chuv.ch.
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Bize
authors.affiliation: Departments of Radiology and Interventional Radiology, CHUV Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: alban.denys@chuv.ch.
authors.forename: Alban
authors.initials: A
authors.lastname: Denys
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland. Electronic address: gerrit.borchard@unige.ch.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland. Electronic address: olivier.jordan@unige.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
mesh_terms: D065546:Drug Liberation; D004621:Embolization, Therapeutic / Q000379:methods*; D066298:In Vitro Techniques; D007211:Indoles / Q000032:analysis*; D008863:Microspheres; D011758:Pyrroles / Q000032:analysis*; D000077210:Sunitinib; D013997:Time Factors
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Chemoembolization; Drug-eluting beads; In vitro drug release; In vitro–in vivo correlation; Sunitinib; Sunitinib (Sutent) PubChem CID: 5329102; USP dissolution apparatus 4