Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved drug stability. One promising group of controlled and targeted drug delivery systems is polymer-based nanoparticles that can sustain the release of the active agent by diffusion and their degradation. Sorafenib is the only drug that can prolong the life of patients suffering from hepatocellular carcinoma. Cisplatin remains one of the most widely used broad-spectrum anticancer drugs for the treatment of a variety of solid tumours. Nanoformulations can exert a synergistic effect by entrapping two drugs with different modes of action, such as sorafenib and cisplatin. In our study, polymeric nanoparticles were prepared with a good production yield by an improved double emulsion solvent evaporation method using the copolymer of 12-hydroxystearic acid with ε-caprolactone (12CL), a biocatalytically synthesised biocompatible and biodegradable carrier, for the co-entrapment of sorafenib and cisplatin in nanotherapeutics. A bovine serum albumin (BSA) model compound was used to increase the cisplatin incorporation; then, it was successfully substituted by a iRGD tumour penetrating peptide that might provide a targeting function of the nanoparticles

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