Encapsulation of a hydrophobic drug in polyphosphate-based nanocarriers

摘要

Thanks to their biocompatibility and degradability properties, polyphosphates are appealing polymers for biomedical applications, especially for drug delivery systems. In contrast to aliphatic polyesters, such as poly(ε-caprolactone) and poly(lactide), the pentavalency of phosphorus atom allows the easy modification of the polyphosphate properties by simply adjusting the nature, the length and the functionality of the polyphosphate pendant groups. Poly(ethylene glycol) (PEG)-b-polyphosphate block copolymers made of hydrophilic PEG and hydrophobic polyphosphates are amphiphilic copolymers prone to self-assemble in aqueous medium into micelles. In order to enhance the encapsulation of hydrophobic drugs, a series of amphiphilic PEG-b-polyphosphate copolymers were synthesized by organocatalyzed ring-opening polymerization of cyclic phosphates and, in some case, followed by thiol-ene click post-polymerization reactions between the pendant vinyl group of a preformed polyphosphate block and some thiols (i.e. dodecyl thiol and tocopherol thiol). Our work aims at changing the nature of the pendant groups of the polyphosphate block to investigate the influence of this structural modification (ⅰ) on the size of the micelles, (ⅱ) on the critical aggregation concentration (CAC), (ⅲ) on the loading of an hydrophobic model drug (i.e. ketoconazole) and, finally, (ⅳ) on the release of this drug. As biomedical applications are foreseen, the cytotoxicity of these PEG-b-polyphosphate copolymers were also evaluated by live/dead cell viability assays.