Abstract
Combinatorial drug delivery is a way of advanced cancer treatment that at present represents a challenge for researchers. Here, we report the efficient entrapment of two clinically used single-agent drugs, doxorubicin and sorafenib, against hepatocellular carcinoma. Biocompatible and biodegradable polymeric nanoparticles provide a promising approach for controlled drug release. In this study, doxorubicin and sorafenib with completely different chemical characteristics were simultaneously entrapped by the same polymeric carrier, namely poly(d,l-lactide-co-glycolide) (PLGA) and polyethylene glycol-poly(d,l-lactide-co-glycolide) (PEG-PLGA), respectively, using the double emulsion solvent evaporation method. The typical mean diameters of the nanopharmaceuticals were 142 and 177 nm, respectively. The PLGA and PEG-PLGA polymers encapsulated doxorubicin with efficiencies of 52% and 69%, respectively, while these values for sorafenib were 55% and 88%, respectively. Sustained drug delivery under biorelevant conditions was found for doxorubicin, while sorafenib was released quickly from the PLGA-doxorubicin-sorafenib and PEG-PLGA-doxorubicin-sorafenib nanotherapeutics.
Highlights
Hepatocellular carcinoma (HCC) is one of the most destructive cancers
Our aim was to synthesize nanocomposites that are capable of encapsulating doxorubicin and sorafenib with high loading, high yield, and high encapsulation efficiency as well as a small size
It must be emphasized that the conditions described in the experimental section were selected after extensive process-optimizing experiments, which included some trials of nanoprecipitation and single emulsion methods
Summary
Sorafenib is the only drug available that prolongs the life of patients with HCC. Non-specific uptake leads to high toxicity and serious side effects. Sorafenib is a multikinase inhibitor that targets various receptor tyrosine kinases and RAF kinases; it hampers tumor growth and exerts cytostatic effects and demonstrates a significant overall survival rate of patients, e.g., with HCC. Its water immiscibility results in low bioavailability [1]; a high dosage is required. Doxorubicin is a common chemotherapeutic agent in numerous cancer therapies [2]. Doxorubicin hydrochloride salt is a water-soluble, hygroscopic, crystalline form of the drug, which possesses better bioavailability. The most disadvantageous side effects of doxorubicin are myelosuppression and cardiotoxicity
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