Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems
Stéphanie Vanslambrouck,
Raphaël Riva,
Bernard Ucakar,
Véronique Préat,
Mick Gagliardi,
Daniel G. M. Molin,
Philippe Lecomte,
Christine Jérôme
Affiliations
Stéphanie Vanslambrouck
Center for Education and Research on Macromolecules (CERM), CESAM Research-Unit, University of Liège, Allée du 6 août 13, B6a, Sart-Tilman, 4000 Liège, Belgium
Raphaël Riva
Center for Education and Research on Macromolecules (CERM), CESAM Research-Unit, University of Liège, Allée du 6 août 13, B6a, Sart-Tilman, 4000 Liège, Belgium
Bernard Ucakar
Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier, 73, B1.73.12, 1200 Brussels, Belgium
Véronique Préat
Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, Université Catholique de Louvain, Avenue Mounier, 73, B1.73.12, 1200 Brussels, Belgium
Mick Gagliardi
Department of Physiology, Faculty of Health, Medicine and Life Science, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
Daniel G. M. Molin
Department of Physiology, Faculty of Health, Medicine and Life Science, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
Philippe Lecomte
Center for Education and Research on Macromolecules (CERM), CESAM Research-Unit, University of Liège, Allée du 6 août 13, B6a, Sart-Tilman, 4000 Liège, Belgium
Christine Jérôme
Center for Education and Research on Macromolecules (CERM), CESAM Research-Unit, University of Liège, Allée du 6 août 13, B6a, Sart-Tilman, 4000 Liège, Belgium
Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.
