Development of curcumin lipid formulations for food applications: transport, permeability and safety evaluation on a mucus-secreting intestinal epithelial cell model

Curcumin is the main phenolic pigment extracted from turmeric, the powdered rhizome of Curcuma longa. It has been shown to exhibit antioxidant, antimicrobial, anti-inflammatory and anticarcinogenic activities however as health promoting agent, curcumin, is limited by its poor solubility in aqueous solution and its low bioavailability and therefore cannot be widely used in food and pharmaceutical processing industry. The challenge addressed in this work was to produce curcumin formulations to enhance its characteristics and evaluate its permeability, transport and cytotoxicity on a stablished in vitro cell co-culture model that mimics the intestinal epithelium. Solid lipid nanoparticles (SLN) and microparticles (SLM) have been visualised as a promising platform on development of formulations for food applications. Since traditional production methods possess a series of limitations, the processing by “green technologies” like supercritical carbon dioxide (scCO2) has been widely investigated. Through Particles from Gas Saturated Solutions (PGSS®) process, beeswax microparticles loaded with curcumin (9:1 (w/w)) were produced and characterized in terms of physicochemical properties: size, morphology, curcumin content and particles dispersion index. Operation process parameters were optimized and defined via response surface methodology and the best response was achieved at 160 bar, 73°C and 10% curcumin load. Under these conditions, encapsulation efficiency was 89.75 ± 2.23 % with a curcumin load of 8.98 % (w/w). Curcumin formulations underwent a digestive process and were tested for their cytotoxicity in Caco-2 monolayer. A triple co-culture has been established and characterized for use as an in vitro intestinal model. To closely mimic the intestinal epithelium the production of mucus by the HT29-MTX-E12 cell line cultured together with the Caco-2 enterocytes and M-cells like phenotype was observed. The model was used to evaluate the transport and permeability of free and encapsulated curcumin and its permeability was stablished as a value of 1.0 x 10-7 cm/s