Dual drug delivery of curcumin and niclosamide using PLGA nanoparticles for improved therapeutic effect on breast cancer cells

Abstract

A number of potent chemopreventives like curcumin and niclosamide have shown promising activities in cancer, although having the drawback of poor bioavailability. To improve the utility of these drugs in cancer therapy, we have encapsulated curcumin and niclosamide in poly(lactic-co-glycolide) (PLGA) nanoparticles, in the presence of poly(vinyl alcohol), using the nanoprecipitation method. We successfully synthesised spherical PLGA nanoparticles, either with each of the single drug individually or with both drugs together, for dual drug loaded samples. FTIR spectroscopy confirmed the successful loading of curcumin and niclosamide in PLGA nanoparticles. The encapsulation efficiency was 48.15% and 70.27% for curcumin and niclosamide, respectively, when loaded individually; which increased to 58.09% for curcumin and 85.36% for niclosamide, with simultaneous dual drug encapsulation. In vitro drug release showed that, as required, a much higher amount of drug released at the acidic pH 6.0 of cancer cells (86.01%, 95.04%, for curcumin and niclosamide, respectively), compared to normal, healthy cell’s pH of 7.4 (25.70% and 60.92% for these two same drugs). MTT assay revealed that dual-drug loaded PLGA nanoparticles exhibited a higher anticancer effect, compared to a bare mixture of two drugs in DMSO (having no PLGA). Therefore, PLGA nanoparticles can be used as an effective carrier to deliver the two hydrophobic drugs to MDA-MB-231 breast cancer cells, for a superior anticancer effect.