Abstract
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 (Cmax, Tmax and AUC0-24) 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.
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•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.