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.

Dual drug-loaded nanotherapeutics can play an important role against the drug resistance and side effects of the single drugs. Doxorubicin and sorafenib were efficiently co-encapsulated by tailor-made poly([R,S]-3-hydroxybutyrate) (PHB) using an emulsion–solvent evaporation method. Subsequent poly(ethylene glycol) (PEG) conjugation onto nanoparticles was applied to make the nanocarriers stealth and to improve their drug release characteristics. Monodisperse PHB–sorafenib–doxorubicin nanoparticles had an average size of 199.3 nm, which was increased to 250.5 nm after PEGylation. The nanoparticle yield and encapsulation efficiencies of drugs decreased slightly in consequence of PEG conjugation. The drug release of the doxorubicin was beneficial, since it was liberated faster in a tumor-specific acidic environment than in blood plasma. The PEG attachment decelerated the release of both the doxorubicin and the sorafenib, however, the release of the latter drug remained still significantly faster with increased initial burst compared to doxorubicin. Nevertheless, the PEG–PHB copolymer showed more beneficial drug release kinetics in vitro in comparison with our recently developed PEGylated poly(lactic-co-glycolic acid) nanoparticles loaded with the same drugs.

Interferon-beta-1a (IFN-β-1a) can diminish the symptoms of relapsing-remitting multiple sclerosis. Herein, we prepared sustained drug delivery IFN-β-1a-loaded nanoparticles by a double emulsion solvent evaporation method. Bovine serum albumin (BSA) model drug was used to optimize the preparation of nanoparticles composed of four types of poly(lactic-co-glycolic acid) (PLGA) polymers and two pegylated PLGA (PEG-PLGA) polymers. Via optimization, selected PLGA and PEG-PLGA polymers were able to entrap IFN-β-1a with high encapsulation efficiency (>95%) and low size (145 nm and 163 nm, respectively). In vitro release kinetics of BSA and IFN-β showed similar tendency for PLGA and PEG-PLGA nanoparticles, respectively. Although the drug loaded nanoparticles did not show toxicity in hepatocyte cells, mild toxic effects such as pale kidney and pyelectasis were observed in the in vivo studies.

Aim: Interferon alpha (IFN-α) controlled release of nanoparticles was investigated under in vitro conditions. Materials & methods: IFN-α and pegylated IFN-α (PEG-IFN-α) were encapsulated by poly(lactic-co-glycolic acid) (PLGA) and pegylated PLGA (PEG-PLGA) copolymers using double emulsion solvent evaporation method. Results: The size of resulting four nanoparticles (IFN-α in poly(lactic-co-glycolic acids), IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol, PEG-IFN-α in poly(lactic-co-glycolic acids) and PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol) was below 130 nm diameter. IFN-α encapsulation efficiency of the nanoparticles was between 78 and 91%. Conclusion: The in vitro drug release studies conducted in phosphate-buffered saline and human plasma highlighted the role of incubation medium on the IFN release from the nanoparticles. The PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol was the most promising nanoparticle among the four formulations because of its re...