We compare the microfluidic manufacturing of polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles (NPs) in a single-phase staggered herringbone (SHB) mixer and in a two-phase gas-liquid segmented mixer. NPs generated from two different copolymer compositions in both reactors and at three different flow rates, along with NPs generated using a conventional bulk method, are compared with respect to morphologies, dimensions, and internal crystallinities. Our work, the first direct comparison between alternate microfluidic NP synthesis methods, shows three key findings: (i) NP morphologies and dimensions produced in the bulk are different from those produced in a microfluidic mixer, whereas NP crystallinities produced in the bulk and in the SHB mixer are similar; (ii) NP morphologies, dimensions, and crystallinities produced in the single-phase SHB and two-phase mixers at the lowest flow rate are similar; and (iii) NP morphologies, dimensions, and crystallinities change with flow rate in the two-phase mixer but not in the single-phase SHB mixer. These findings provide new insights into the relative roles of mixing and shear in the formation and flow-directed processing of polymeric NPs in microfluidics, informing future reactor designs for manufacturing NPs of low polydispersity and controlled multiscale structure and function.

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We demonstrate flow-directed production of nanoparticles of the photoresponsive block copolymer poly(onitrobenzyl acrylate)-b-polydimethylacrylamide in a gas−liquid microfluidic reactor. Microfluidic formation produced a variety of morphologies dependent on flow rate, with spheres and short cylinders, then large compound micelles, then unique spooled cylinders appearing as flow rate increased. The higher excess free energy of spooled cylinders relative to the quiescent equilibrium state is evidenced by their faster off-chip relaxation times (∼1 day) as compared to other flow-directed structures. Comparison of light-triggered dissociation of flow-directed nanoparticles prepared at two different flow rates shows faster disruption of nanoparticles prepared at the higher flow rate. The application of variable flow to direct both structure and responsivity suggests interesting possibilities for controlled microfluidic manufacturing of "smart" polymeric colloids.

The synthesis, characterization, and self-assembly of a series of biocompatible poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) amphiphilic block copolymers with variable MCL contents in the hydrophobic block are described. Self-assembly gives rise to polymeric nanoparticles (PNPs) with hydrophobic cores that decrease in crystallinity as the MCL content increases, and their morphologies and sizes show nonmonotonic trends with MCL content. PNPs loaded with the anticancer drug paclitaxel (PAX) give rise to in vitro PAX release rates and MCF-7 GI50 (50% growth inhibition concentration) values that decrease as the MCL content increases. We also show for selected copolymers that microfluidic manufacturing at a variable flow rate enables further control of PAX release rates and enhances MCF-7 antiproliferation potency. These results indicate that more effective and specific drug delivery PNPs are possible through tangential efforts combining polymer synthesis and microfluidic manufacturing.