Poly(glycerol sebacate) nanoparticles for encapsulation of hydrophobic anti-cancer drugs

Physical encapsulation of hydrophobic compounds into nanocarriers that are stable in aqueous medium is of high interest as it can increase solubilization of the drug, lower its toxicity, control its pharmacokinetic profile and thus overall improve the therapeutic efficacy. To increase solubilization of a drug in aqueous medium, the carrier should contain hydrophobic domains that can form non-covalent interactions with hydrophobic drug molecules. Apart from liposomes, polymers have been widely acknowledged as promising nanocarriers. In this paper, we report the design of poly(glycerol sebacate) (PGS), an inexpensive, water insoluble but biodegradable and biocompatible polymer, into nanocarriers for hydrophobic drugs. Mixing of alcoholic PGS solutions with water (i.e. solvent displacement) produced a fine and highly stable dispersion with a size that can be controlled by the PGS concentration and solvent to water ratio. These dispersions were used for the encapsulation of hydrophobic compounds such as a fluorescent dye and two drugs known for their anti-mitotic activity (i.e. paclitaxel (PTX) and flubendazole (FLU)). These formulations were then evaluated in vitro with cancer cells.