Abstract
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 °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 μg/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.
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•DOX and NAR loaded PLGA-NPs (F3) and CS-coated PLGA-NPs (F4) was prepared.•CS-coating on PLGA-NPs converted its low negative surface charge to high positive.•Sufficient encapsulation and loading of DOX and NAR were found in F3 and F4.•In vitro profiling indicated sustained release of both the drugs from F3 and F4.•F4 was highest cytotoxic as compared to F3, DOX-NAR aqueous suspension and DOX alone.