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

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

Córdoba

Congreso; VIII Congreso Internacional de Ciencia y Tecnología de Alimentos (CICYTAC 2022); 2022

Curcumin (CCM) is a naturalpolyphenol traditionally used as spice and food coloring. It is also considereda nutraceutical with many demonstrated properties: antioxidant,anti-inflammatory, anticancer, antiprotozoal, antiviral and antibacterial.However, despite these beneficial properties, the extreme low solubility of CCMin water limits its bioavailability and, at the same time, impedes itsinclusion in functional foods and beverages. Therefore, the encapsulation ofCCM in hydrophilic carriers is highly desirable. In particular, the binding ofCCM to soluble proteins is a promising alternative for better bioavailability.Microfluidic techniques enable the implementation of low energy and continuumprocesses, with fast mass transfer and homogeneous mixing at the microscale.Here, we describe the microfluidic generation of CCM-loaded albuminnanoparticles (NPs) using devices designed to produce solvent-shiftingnanoprecipitation byhydrodynamic focusing in cylindrical capillaries (core-sheath flows). Two coaxial fluid streams wereforced to co-flow as core and sheath fluids along the capillary tube. Theethanol stream containing CCM (inner fluid) was squeezed by the aqueous proteinsolution (outer fluid). Interdiffusion across the core-sheath interface enabledrapid mixing and the consequent solvent shifting, which triggered thenucleation of precursors and the growth of nanoparticles. Microfluidicdevices were fabricated by assembling the following components: stainless steeldispensing needles, transparent tee connectors, Teflon tubing, and silicontubing 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. The innerfluid was the organic solution of CCM, injected at the flow rate QCCM, which washydrodynamically focused by the outer fluid, the aqueous solution of α-LA,injected at the flow rate Qα-LA. Both fluids were injected using a hydrostatic 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 NPs size wasevaluated by DLS. It was observed that NPs size decreased with both, the flow rate ratio andthe total flow rate. These results showed that the microfluidic technique allowsone to adjust the diameter of NPs by controlling the flow rates of theprecursor fluids. Then, the optimal operation conditions selected to CCM-α-LA NPsproduction were: Q α-LA/QCCM =10 and QCCM +Q α-LA= 20 mL/h. The obtained NPs with an averagediameter of 181±3nm resulted highly monodisperse and presented an encapsulationefficiency of 43±1.4% quantified by UV−visible spectrophotometry. Scanning electron and transmission electron microscopy imagesshowed that NPs where spherical, uniformlydispersed and presented well-defined borders. In vitro CCM release studywas evaluated in PBS (pH 6.8) during 4 h and it was observed that the 74% ofthe 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.