Fabrication of the quaternary nanocomplex curcumin-casein-alginate-chitosan as a potential oral delivery system for cancer nutraceutical therapy

Fabricating a nanocargo made from natural constituents for delivering the anticancer drug curcumin orally may offer hope for cancer patients. In this study, protein and polysaccharides were conjugated to form curcumin-loaded casein nanoparticles coated with alginate and chitosan as a double polysaccharide layer “Alg-ch@CurCasNPs”. The developed nanoformulation was characterized in vitro, and its pharmacokinetics and therapeutic efficacy against Ehrlich carcinoma were assessed in vivo. Alg-ch@CurCasNPs exhibited high curcumin encapsulation efficiency (EE = 70%) and controlled release in gastric and intestinal environments. The measured size distribution and zeta potential were 240 ± 20 nm and ±35 mV, respectively. The Alg-ch@CurCasNP morphology showed a monodispersed sphere with a double layer coating. The in vivo pharmacokinetic parameters (C max , T max and AUC 0-24 ) for Alg-ch@CurCasNPs were significantly better than those for free curcumin (Curfree). The in vivo integrated results, including the tumor inhibitory rate (IRT%), genotoxicity and tumor histopathology, collectively demonstrated that repeated oral administration of Alg-ch@CurCasNPs (6 doses/2 weeks-600 mg/kg) in mice showed higher therapeutic efficacy against Ehrlich carcinoma than Curfree treatment. Overall, Alg-ch@CurCasNPs are natural quaternary nanocomplexes that can deliver curcumin orally, enhance its bioavailability and achieve a high therapeutic index in the treatment of cancer. • Natural nanodelivery system composed of curcumin -casein- alginate-chitosan was synthesized. • The developed oral nano delivery system enhances curcumin pharmacokinetics. • The oral nanocomplex system overcomes gastric barrier and safely reaches the intestine region. • The developed nanocargo enhances curcumin bioavailability and cancer therapeutic efficacy against Ehrlich carcinoma.