Engineering of nanoparticle size via electrohydrodynamic jetting

Abstract

Engineering the physical properties of particles, especially their size, is an important parameter in the fabrication of successful carrier systems for the delivery of therapeutics. Here, various routes were explored for the fabrication of particles in the nanosize regime. It was demonstrated that the use of a charged species and/or solvent with high dielectric constant can influence the size and distribution of particles, with the charged species having a greater effect on the size of the particles and the solvent a greater effect on the distribution of the particles. In addition to the fabrication of nanoparticles, their fractionation into specific size ranges using centrifugation was also investigated. The in vitro particle uptake and intracellular transport of these nanoparticles was studied as a function of size and incubation period. The highest level of intralysosomal localization was observed for the smallest nanoparticle group (average of 174 nm), followed by the groups with increasing sizes (averages of 378 and 575 nm), most likely due to the faster endosomal uptake of smaller particles. In addition, the internalization of nanoparticle clusters and number of nanoparticles per cell increased with longer incubation periods. This work establishes a technological approach to compartmentalized nanoparticles with defined sizes. This is especially important as relatively subtle differences in size can modulate cell uptake and determine intercellular fate. Future work will need to address the role of specific targeting ligands on cellular uptake and intracellular transport of compartmentalized nanoparticles.

Spatial Analysis of Metal–PLGA Hybrid Microstructures Using 3D SERS Imaging

“…The final particle size was influenced by the solvent composition and the molecular weight of PLGA. [19] When using 17 kDa PLGA and 70:30 CHCl 3 :DMF, particles of ≈600-800 nm were obtained, whereas 40 kDa PLGA in 70:30 CHCl 3 :DMF yielded particles of ≈1-2 µm, and using 50-75 kDa PLGA and solvent ratios between 70:30 and 97:3 CHCl 3 :DMF, particles in the range of 3-8 µm could be produced.…”

“…[16] In this context, poly(lactic-co-glycolic acid) (PLGA) is a biocompatible (FDA approved) [17] and biodegradable polymer, which is widely used to fabricate nanostructures like microgels, nanoparticles, fibers, or rods. [18,19] PLGA can also be loaded with drugs and functional molecules for further surface functionalization. [20,21] Additional complexity has also been imparted to PLGA nanostructures by implementing multicompartmental structures for highly specific applications, such as drug delivery systems containing two different drugs and distinct release profiles.…”

“…This process has been well established for PLGA over the last decade and offers a high throughput method to synthesize PLGA microgels of different sizes and morphologies. [19] Transfer of gold nanoparticles from water into chloroform (CHCl 3 ) [6,30] was accomplished using hydrophobic SERS active molecules, which act as both capping agents and SERS labels. The resulting nanoparticles with high and reliable SERS signals can be embedded in selected compartments of the PLGA particles, while different fluorescent dyes were added to other compartments, thereby allowing us to expand the standard characterization methods (transmission electron microscopy (TEM), scanning electron microscopy (SEM), and fluorescence microscopy) and using 3D confocal SERS microscopy (3D-SERS) to identify the nanoparticle distribution inside the polymer.…”

Compartmentalized Microhelices Prepared via Electrohydrodynamic Cojetting

“…Specific applications range from sensors,3 drug delivery vehicles,4 surfactants,2, 5 and catalysts6 to soft microactuators 7. This progress has been enabled by an arsenal of methods for the fabrication of compartmentalized microparticles have been developed, such as stop‐flow lithography by Doyle and co‐workers,8 droplet microfluidics by Weitz's groups,9 or the PRINT method by DeSimone and co‐workers 10.…”

“…This progress has been enabled by an arsenal of methods for the fabrication of compartmentalized microparticles have been developed, such as stop‐flow lithography by Doyle and co‐workers,8 droplet microfluidics by Weitz's groups,9 or the PRINT method by DeSimone and co‐workers 10. Similarly, electrohydrodynamic (EHD) cojetting has been widely used for preparing multicompartmental microbuilding blocks 2, 3, 4, 5, 6, 7, 11, 12, 13…”