High Throughput Block Copolymer Micelle Assembly Methods and Morphologies

Block copolymer micelles hold tremendous potential in the biomedical and materials science fields, with uses ranging from drug delivery to new methods of lithography. Micelles are an attractive technology for these applications because of their ease of assembly and tunable properties. Typical micelles are nanoscale structures with hydrophobic cores and hydrophilic coronae. Smaller nanomaterials can be loaded in the core, thus allowing aqueous delivery of otherwise hydrophobic payloads. To date, most micellar research has focused on bench-scale development, rather than translation of this technology to industrial processes. Flexible, high throughput manufacturing strategies for micellar production are necessary for commercialization.

Here, we describe and compare two promising semi-continuous methods for synthesis of inorganic-polymer composite micelle nanoparticles. The first combines a scalable electrospray technique with an interfacial instability process to form micellar structures. The second is an adaptation of a flash nanoprecipitation technique originally developed by Prud’homme and colleagues as a way to more rapidly generate polymer aggregates.

In the electrospray method, separate and immiscible aqueous and polymer-in-organic solutions flow through a thin coaxial needle assembly, and voltage is applied until a cone-jet spray forms. Aerosol particles are ejected from the spray, travel through the air, and are collected in water as emulsion droplets that undergo transient interfacial surface tension changes, resulting in micelle formation. Here, we explored the limits of the coaxial electrospray process by varying operational parameters to achieve higher polymer processing and throughput, thus accessing greater nanoparticle yields. We independently evaluated the influence of electrospray volumetric flow rates, organic block copolymer loading, and system processing temperature on micelle formation and processing rates for the polymer polystyrene-block-poly(ethylene oxide) (PS-b-PEO). Using this approach, we increased production rates by a factor of 40 over previous reports and accessed different assembly morphologies.

We compared this process to the flash nanoprecipitation method. In this method, water is rapidly mixed with block copolymers in a water miscible solvent (i.e., tetrahydrofuran). We studied polymer nanoparticle formation for both PS-b-PEO and poly(ethylene glycol)-block-polycaprolactone (PEG-PCL), and demonstrated micelle production at different mixing speeds, allowing flexibility of production at rates higher than observed using micellar electrospray.

Both micelle production techniques hold promise for the formation of empty and loaded micelles of different morphologies. Micellar electrospray is preferred for use with longer block copolymers because of the high mixing rates required in flash nanoprecipitation. However, flash nanoprecipitation is a faster method for appropriate molecules. Each synthesis system has potential application in drug delivery, imaging, diagnostics, and separations.