Abstract
The synthesis of Zein nanoparticles (NPs) using conventional methods, such as emulsion solvent diffusion and emulsion solvent evaporation, is often unreliable in replicating particle size and polydispersity between batch-to-batch syntheses. We have systematically examined the parameters for reproducibly synthesizing Zein NPs using a Y-junction microfluidics chip with staggered herringbone micromixers. Our results indicate that the total flow rate of the fluidics system, relative flow rate of the aqueous and organic phase, concentration of the base material and solvent, and properties of the solvent influence the polydispersity and size of the NPs. Trends such as increasing the total flow rate and relative flow rate lead to a decrease in Zein NP size, while increasing the ethanol and Zein concentration lead to an increase in Zein NP size. The solvent property that was found to impact the size of the Zein NPs formed the most was their hydropathy. Solvents that had a hydropathy index most similar to that of Zein formed the smallest Zein NPs. Synthesis consistency was confirmed within and between sample batches. Stabilizing agents, such as sodium caseinate, Tween 80, and Pluronic F-68, were incorporated using the microfluidics system, necessary for in vitro and in vivo use, into Zein-based NPs.
Highlights
Nanoparticle-based drug delivery systems have been investigated over the past few decades to improve the efficacy, bioavailability, and circulation half-life of small molecule drugs [1,2].Modulating the particle0 s size and shape changes its biodistribution, and allows control over the pharmacokinetics of the loaded drug
Tween 80 (TW80) and F-68 samples were used as the aqueous phase and Zein was present in the organic phase (60% ethanol) in the microfluidic system
Zein NPs form according to the basic principles of a liquid–liquid dispersion (LLD) process; the soluble phase containing Zein is introduced to the bulk insoluble phase
Summary
Nanoparticle-based drug delivery systems have been investigated over the past few decades to improve the efficacy, bioavailability, and circulation half-life of small molecule drugs [1,2]. Coprecipitation, a particle formulation method based on a protein0 s differential solubility in two solvents, is commonly used to produce protein NPs, including Zein. To modulate the size and polydispersity of the NPs, parameters such as the relative flow microfluidic systems scalable andthe show potential the production at industrial rate of the aqueous andare organic phase, totalgood flow rate of the for fluidics system, andof theNPs properties of the scales [26]. There are few systematic studies on the reproducibility of microfluidics for preparing protein NPs, Wesystem report here the usethat of Y-channel chips with staggered herringbone micromixers and the parameters affect the microfluidic size and polydispersity of the particles.
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