Chitosan-coated poly (lactic-co-glycolide) nanoparticles for dual delivery of doxorubicin and naringin against MCF-7 cells

Present investigation examines the simultaneous encapsulation and delivery of DOX and NAR through PLGA-NPs and CS-coated PLGA-NPs to improve the efficacy and synergistic anticancer activity of DOX, and reduce its toxicity. Drug-loaded F3 and F4 were prepared by double-emulsion solvent-evaporation technique. PS, PDI, ZP and morphology of the NPs were determined using Zetasizer and SEM, respectively. %EE and %DL of both drugs were determined by indirect method. Dialysis tubing was used for in vitro release studies in phosphate buffer saline (pH 6.8) with SLS (0.1% w/v). Storage stability of the NPs was performed at 30 degrees C for 6-months. In vitro cytotoxicity was determined by MTT-assay, using MCF-7 cells. Cytotoxic effects of the NPs were also observed by visualizing the morphological changes in MCF-7 cells. PS, PDI and ZP of F4 were 366.8 +/- 36.7 nm, 0.352 +/- 0.033 and +35.57 +/- 4.25 mV, respectively and those of F3 were 302.2 +/- 45.4 nm, 0.283 +/- 0.016 and -4.69 +/- 2.66 mV. Increased PS and high positive ZP were found after CS-coating. Smooth-surfaced PLGA-NPs were observed by SEM, and slightly rough-surfaced NPs were found after CS-coating. %EE and %DL for DOX were 66.01%, 4.26% and 76.26%, 3.28% in F3 and F4, respectively. For NAR, these values were 77.82%, 3.22% and 71.85%, 4.64% in F3 and F4. The in vitro release profile revealed a sustained delivery of the drugs with 51% and 63% of DOX, as well as 80% and 78% of NAR at 48 h, from F3 and F4, respectively. Relatively high amounts of DOX and NAR were rapidly released from DOX-NAR-AqS at 2 h only. Release kinetic investigations justify the sustained release property of F3 and F4, and they followed the "Korsmeyer-Peppas model". Release-exponent values suggest that the mechanism of the drug(s) release was Fickian-diffusion. Stability study revealed acceptable physicochemical changes for 6-months F4 showed the highest cytotoxicity (IC50, 1.52 mu g/mL), when compared to F3, free DOX-NAR combination and DOX alone. Cytotoxicity and cell morphology represented the highest cellular uptake of F4. Conclusively, F4 could be an effective nano-carrier for DOX and NAR to improve their encapsulation, sustain their release, stability and simultaneous delivery against MCF-cells.