We apply gas-liquid microfluidic reactors containing flow-variable, high-shear "hot spots" to produce curcumin-loaded polymer nanoparticles (CUR-PNPs) comprised of poly(caprolactone)- block-poly(ethylene oxide) (PCL- b-PEO) block copolymers at various flow rates and CUR loading ratios. CUR-PNPs prepared using the conventional nanoprecipitation method (bulk method) showed decreased encapsulation efficiency and increased drug precipitation as the loading ratio increased. However, CUR-PNPs prepared by microfluidic manufacturing showed both increased encapsulation efficiency and increased drug loading as either the flow rate or the loading ratio increased. This enabled microfluidic CUR loading percentages of up to 30% to be achieved in this study, which to our knowledge is a record for block copolymer PNPs. As well, it is shown that increased flow rate of microfluidic manufacturing leads to decreased mean CUR-PNP sizes (down to ∼50 nm) and narrower size distributions, along with significantly different CUR release kinetics compared to CUR-PNPs prepared at slower flow rates. In vitro antiproliferation experiments against MDA-MB-231 cells give an average IC50 value of 24 μM for CUR-PNPs compared to 13 μM for free CUR at the same incubation time of 72 h. Compared to conventional bulk and single-phase microfluidic strategies, this unique two-phase reactor represents an exciting manufacturing platform for optimizing polymeric CUR nanomedicines though flow-directed shear processing.
Keywords: curcumin; drug delivery; microfluidics; polymer nanoparticles.