Biocatalytic synthesis of poly[ε-caprolactone-co-(12-hydroxystearate)] copolymer for sorafenib nanoformulation useful in drug delivery

Nanoformulations can play an important role in the improvement of anticancer drug therapies. The bioavailability of sorafenib, which is the exclusively applied drug in the treatment of unresectable hepatocellular carcinoma, may be increased by its incorporation in a biocompatible nanoparticulate matrix that is capable of targeting and controlling the drug release. The copolymers of ε-caprolactone are emerging biodegradable compounds for drug delivery applications. In this work, an immobilized lipase and three native hydrolases, a lipase, an esterase and a protease (two of them not previously used as polyesterification catalysts) have been studied as biocatalysts for the synthesis of oligomers of ε-caprolactone and 12-hydroxystearic acid, proving different selectivity regarding the polymerization degree, ratio of linear and cyclic oligomers, and insertion of the fatty acid units in the polymeric chain. The synthesized poly[ε-caprolactone-co-(12-hydroxystearate)] was used as a novel encapsulating copolymer for preparation of sorafenib-loaded polymeric nanocomposites. The nanoparticle formulation by emulsion-solvent evaporation method was optimized for particle size and encapsulation efficiency. The developed nanotherapeutics showed promising drug release profile and cytotoxic effect in vitro in HepG2 hepatocellular cells.