Nitogenin-PEG succinate micelles for curcuminoid delivery: synthesis, in vitro cytotoxicity, and in vivo pharmacokinetics.

In the present study, three kinds of curcuminoids (CS)-loaded micelles (CS-NPGS) were prepared by the solid dispersion method using novel Nitogenin polyethylene glycol succinate-1000 (NPGS-1000) to enhance the solubility and bioavailability. The micelles were characterized using a particle size analyzer, a crystallography analyzer, and Fourier transform infrared spectroscopy (FT-IR). The morphology was screened using a scanning electron microscope. In vitro release profiles of curcumin from CS-NPGS showed a sustained release without rapid burst. Treating triple negative MDA-MB-231 cell lines with all micelles remarkably exhibited dose-dependent toxicity and inhibited the cell proliferation. Epifluorescence was used to evaluate the morphology of the treated cells by using various stains. The IC50 values of the curcumin-loaded micelles against triple negative MDA-MB-231 cells were 10.85, 5.43, and 5.43 μg/mL for CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3, respectively, lower than the one of free curcumin (21.7 μg/mL). An in vivo rat oral pharmacokinetic study showed 13.25×, 16.43×, and 18.51× increases in Cmax for CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3 compared to curcuminoid powder, respectively. The relative bioavailability of CS-NPGS-1, CS-NPGS-2, and CS-NPGS-3 was 155.21%, 504.82%, and 687.83% compared to CS, respectively. The aqueous solubility of encapsulated CS-NPGS micelles is considerably improved, allowing for more localized drug delivery and a superior treatment alternative for residual cancer tumors.