Co-entrapment of sorafenib and cisplatin in poly[ε-caprolactone-co-(12-hydroxystearate)] copolymer for dual drug delivery application

Drug-loaded nanocarriers have overcome various challenges compared with the bare chemo-drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, adverse drug reactions, particularly side effects of chemotherapy and offer 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 the polymer-based nanoparticles which can sustain release of active agent by diffusion and their degradation. Sorafenib is the only drug which is capable to prolong the life of patients suffered from Hepatocellular carcinoma. Cisplatin remains one of the most widely used broad spectrum anticancer drug for the treatment of a variety of solid tumors. Nanoformulations can exert synergistic effect by entrapping two drugs with different mode of action, such as sorafenib and cisplatin. In our study, we prepared polymeric nanoparticles by optimised double emulsion solvent evaporation method with a good production yield by a novel biocatalytically synthetized 12-hydroxystearic acid e-caprolactone copolymer (12CL) which is biocompatible and biodegradable carrier by co-entrapment of sorafenib and cisplatin in nanotherapeutics in order to investigate the synergistic effect of sorafenib in combination with cisplatin. The active agents were encapsulated and also cross-linked with carbodiimide to increase the encapsulation efficiency. To improve the drug encapsulation efficiency, bovine serum albumin (BSA) was also incorporated as a protein capable of complexation with the cisplatin.