title: Arming embolic beads with anti-VEGF antibodies and controlling their release using LbL technology.
abstract: Transarterial chemoembolization (TACE) is used to treat various types of hypervascular tumors such as hepatocellular carcinoma and renal cancer. However, embolization and blocking of blood vessels nourishing a tumor mass evokes an angiogenic response due to the secretion of vascular endothelial growth factor (VEGF), which results in the formation of new blood vessels and eventually limitation in therapeutic efficacy. The presented work investigates the feasibility of loading the clinically used embolic beads (DC Bead®) with Bevacizumab (BEV), an anti-VEGF antibody, and control its release kinetics via Layer-by-Layer (LbL) coating. This strategy has the aim to achieve high, localized and sustained concentrations of BEV at the tumor site and reduce drug exposure in the systemic circulation. High loading of BEV on lyophilized beads of about 76mg BEV/bead vial was achieved. LbL coating was carried out by depositing alternating layers of the biocompatible polymers alginate and poly-L-lysine. Coating was proven successful by monitoring the reversal of zeta potential after addition of each layer. Morphological changes of the bead surface before and after coating were illustrated using SEM imaging. Moreover, release profiles from different formulations were studied and results showed that optimizing the number of deposited layers effectively slows the release of BEV for three days. Activity of released BEV was studied in different 2D and 3D cell based assays. Released BEV fractions showed comparable activity to fresh BEV solution used as control after 3days. In conclusion, our results suggest the opportunity for loading anti-VEGF antibodies on commercially available embolic beads to increase the efficacy of TACE of hypervascular tumors.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: O S
authors.initials: OS
authors.lastname: Sakr
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Berndt
authors.affiliation: CRRET Laboratory, University of Paris Est Creteil Val de Marne, Avenue du Général de Gaulle 61, 94010 Créteil Cedex, France.
authors.forename: G
authors.initials: G
authors.lastname: Carpentier
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Cuendet
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Jordan
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: Gerrit.Borchard@unige.ch.
authors.forename: G
authors.initials: G
authors.lastname: Borchard
mesh_terms: D000464:Alginates; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019138:Antibodies, Blocking / Q000008:administration & dosage* / Q000494:pharmacology*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D006801:Humans; D010316:Particle Size; D011107:Polylysine / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000464:Alginates; D020533:Angiogenesis Inhibitors; D019138:Antibodies, Blocking; D003692:Delayed-Action Preparations; D005079:Excipients; D042461:Vascular Endothelial Growth Factor A; D011107:Polylysine; D000068258:Bevacizumab
keywords: 3D angiogenesis; Bevacizumab; Embolic beads; Layer-by-Layer (LbL); Protein delivery; Sustained delivery