Journal
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 93, Issue -, Pages 178-190Publisher
ELSEVIER
DOI: 10.1016/j.msec.2018.07.069
Keywords
Curcumin diglutaric acid; Chitosan; Alginate; Nanoparticles; Cancer
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Funding
- Ratchadapisek Sompoch Endowment Fund (2016), Chulalongkom University [CU-59-031-AM]
- Rachadapisek Sompote Fund
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Curcumin diglutaric acid (CG) is a prodrug of curcumin that shows better solubility and antinociceptive activity compared to curcumin. To improve its properties further, CG was encapsulated into polysaccharide-based nanoparticles in this study. A chitosan/alginate nanoparticulate system was chosen for encapsulation of CG due to its biocompatibility, biodegradability, non-toxicity, mucoadhisiveness and good film formation. CG-loaded chitosan/alginate nanoparticles were prepared by o/w emulsification and ionotropic gelification, with the conditions optimized using response surface methodology. A chitosan/alginate mass ratio of 0.04:1, CG concentration of 3 mg/mL and Pluronics (R) F127 concentration of 0.50% (w/v) were determined to be optimal for the nanoparticle preparation. FUR and XRD confirmed encapsulation of CG into the chitosan/alginate nano particles. The CG-loaded chitosan/alginate nanoparticles showed better stability under UV radiation and in a simulated gastrointestinal environment, compared to a CG dispersion in water. The nanoparticles showed slow cumulative release of CG in simulated gastrointestinal fluids without enzymes and in body fluid. A Weibull model of the best fit for all conditions suggested that the release pattern of CG from CG-loaded chitosan/alginate nanoparticles was mainly controlled by Fickian diffusion and erosion of polymer materials. Finally, CG-loaded chitosan/alginate nanoparticles showed higher in vitro cellular uptake in human epithelial colorectal adenocarcinoma (Caco-2 cells) and better anticancer activity against Caco-2, human hepatocellular carcinoma (HepG2) and human breast cancer (MDA-MB-231) cells. Therefore, the CG-loaded chitosan/alginate nano particles are a promising approach for oral administration of CG for cancer treatment.
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