Abstract
Curcumin is a promising anticancer agent, but its clinical utilization has been hindered by its low solubility and bioaccessibility. To overcome these obstacles, we developed a natural protein-polysaccharide nanocomplex made from casein nanoparticles coated with a double layer of alginate and chitosan and decorated with folic acid (fCs-Alg@CCasNPs) for use as a nanocarrier for curcumin. The developed nanoformulation showed a drug encapsulation efficiency = 75%. The measured size distribution of fCs-Alg@CCasNPs was 333.8 ± 62.35 nm with a polydispersity index (PDI) value of 0.179. The recorded zeta potential value of fCs-Alg@CCasNPs was 28.5 mV. Morphologically, fCs-Alg@CCasNPs appeared spherical, as shown by transmission electron microscopy (TEM). The successful preparation of fCs-Alg@CCasNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy of all the constituents forming the nanoformulation. Further in vitro investigations indicated the stability of fCs-Alg@CCasNPs as well as their controlled and sustained release of curcumin in the tumor microenvironment. Compared with free curcumin, fCs-Alg@CCasNPs induced a higher cytotoxic effect against a pancreatic cancer cell line. The in vivo pharmacokinetics of fCs-Alg@CCasNPs showed a significant AUC0-24 = 2307 ng.h/ml compared to 461 ng.h/ml of free curcumin; these results indicated high curcumin bioavailability in plasma. The in vivo results of tumor weight, the amount of DNA damage measured by comet assay and histopathological examination revealed that treating mice with fCs-Alg@CCasNPs (either intratumorally or intraperitonially) prompted higher therapeutic efficacy against Ehrlich carcinoma than treatment with free curcumin.Therefore, the incorporation of curcumin with protein/polysaccharide/folate is an innovative approach that can synergistically enhance curcumin bioavailability and potentiate cancer therapy with considerable biosafety.
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