Microfluidic generation of curcumin-loaded albumin nanoparticles by solvent-shifting precipitation in core-sheath flows

MINETTI, FLORENCIA; MENGATTO, LUCIANO N.; OLIVARES, MARÍA L.; BERLI, CLAUDIO L.A.

Córdoba

Congreso; VIII Congreso Internacional de Ciencia y Tecnología de Córdoba CICyTAC 2022; 2022

Ministerio de Ciencia y Tecnología de Córdoba

Curcumin (CCM) is a natural polyphenol traditionally used as spice and foodcoloring. It is also considered a nutraceutical with many demonstratedproperties: antioxidant, anti-inflammatory, anticancer, antiprotozoal, antiviraland antibacterial. However, despite these beneficial properties, the extreme lowsolubility of CCM in water limits its bioavailability and, at the same time,impedes its inclusion in functional foods and beverages. Therefore, theencapsulation of CCM in hydrophilic carriers is highly desirable. In particular,the binding of CCM to soluble proteins is a promising alternative for betterbioavailability. Microfluidic techniques enable the implementation of low energyand continuum processes, with fast mass transfer and homogeneous mixing atthe microscale. Here, we describe the microfluidic generation of CCM-loadedalbumin nanoparticles (NPs) using devices designed to produce solvent-shiftingnanoprecipitation by hydrodynamic focusing in cylindrical capillaries (coresheath flows). Two coaxial fluid streams were forced to co-flow as core andsheath fluids along the capillary tube. The ethanol stream containing CCM(inner fluid) was squeezed by the aqueous protein solution (outer fluid).Interdiffusion across the core-sheath interface enabled rapid mixing and theconsequent solvent shifting, which triggered the nucleation of precursors andthe growth of nanoparticles. Microfluidic devices were fabricated by assemblingthe following components: stainless steel dispensing needles, transparent teeconnectors, Teflon tubing, and silicon tubing for fittings. An alpha-lactalbumin(α-LA) solution (0.2% w/v) was prepared in 50mM and pH 7 phosphate buffersaline (PBS). Also, CCM (0.05%w/v) was prepared in ethanol 96% v/v. Theinner fluid was the organic solution of CCM, injected at the flow rate QCCM,which was hydrodynamically focused by the outer fluid, the aqueous solution ofα-LA, injected at the flow rate Qα-LA. Both fluids were injected using ahydrostatic pumping system. The flow regime was completely defined by twocontrolling parameters: the flow rate ratio (Qα-LA /QCCM) and the total flow rate(QCCM +Qα-LA). The independent effects of these fluid dynamic variables on NPssize was evaluated by DLS. It was observed that NPs size decreased with both,the flow rate ratio and the total flow rate. These results showed that themicrofluidic technique allows one to adjust the diameter of NPs by controllingthe flow rates of the precursor fluids. Then, the optimal operation conditions selected to CCM-α-LA NPs production were: Q α-LA /QCCM =10 and QCCM +Q α-LA= 20 mL/h. The obtained NPs with an average diameter of 181±3nm resultedhighly monodisperse and presented an encapsulation efficiency of 43±1.4%quantified by UV−visible spectrophotometry. Scanning electron andtransmission electron microscopy images showed that NPs where spherical,uniformly dispersed and presented well-defined borders. In vitro CCM releasestudy was evaluated in PBS (pH 6.8) during 4 h and it was observed that the74% of the encapsulated CCM was released. It is concluded that the proposedmethodology is a promising route to scale up the microfluidic elaboration ofnanoparticles for the encapsulation of active ingredients.