Abstract
Curcumin (CCM) is a natural compound with strong tumor-inhibiting activity. However, CCM is not widely used for cancer treatment because of its poor water solubility, penetration, and bioavailability. In this study, CCM and piperine (PPR), a bio-enhancer, were co-encapsulated within chitosan (CS) by co-axial electro-spraying method aiming to increase CCM bioavailability. Two formulation approaches have been proposed, including (1) co-encapsulation of CCM and PPR in micro-particle core (e.g., CCM/PPR@CS) and (2) separate encapsulation of CCM and PPR in two different CS layers (e.g., CCM@PPR@CS). The optimal electro-spraying parameters were investigated and found to be applied voltage of 15 kV, flow-rate of 0.1/0.2 mL h− 1 (core/shell), and needle tip-to-collector distance of 10 cm for CCM/PPR@CS micro-particle; and applied voltage of 19 kV, flow rate of 0.1/0.2/0.3 mL h− 1 (inner-layer/middle-layer/outer-layer), and working distance of 14 cm for CCM@PPR@CS formulation. The obtained particles were non-agglomerated, spherical, and possessed core-shell structure with clear boundaries, relatively wide distribution with mean diameters of 366 ± 136 nm for CCM/PPR@CS and 784 ± 139 nm for CCM@PPR@CS. As expected, the in vitro data showed that PPR was released faster than CCM with the separation of PPR and CCM in two different layers, and the drugs were released more strongly at pH 5.5 than at pH 7.4 due to pH sensitivity of chitosan shell. The CCM and PPR cumulative releases were also high (70–80%). In conclusion, the CCM@PPR@CS structure could be utilized as a potential drug delivery system for decreasing denaturation and enhancing the absorption of CCM.