Fluorescence Study of the Effects of Microfluidic Manufacturing Variables on the Microenvironment of a Pyrene Drug Surrogate within Block Copolymer Drug Delivery Vectors.

We used a gas-liquid segmented microfluidic reactor to produce various formulations of polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) polymer nanoparticles (PNPs) containing encapsulated pyrene (Py) as a hydrophobic drug surrogate to evaluate the effects of typical PNP manufacturing variables on the microenvironment of encapsulated molecules. Steady-state fluorescence emission from encapsulated Py was collected for various formulations (variable PCL block length, initial Py-to-copolymer ratio, on-chip water content, and flow rate) and the vibronic emission ratio (I1/I3) and excimer-to-monomer ratio (Ie/Im) were used to assess the polarity and Py aggregation state, respectively, within Py encapsulation sites. Hydrodynamic size distributions, internal crystallinities, and dye loadings of the cores were also evaluated. When the hydrophobic block length and initial Py-to-copolymer ratio were varied, changes in the Py aggregation state correlated with changes in Py concentrations in the core, while high microenvironment polarity suggested strong Py localization at the core-corona interface. On the other hand, when the on-chip water content was varied, Py concentrations in the core remained relatively constant and changes in Py aggregation states correlated with changes in the extent of interfacial localization of encapsulated Py. Finally, when the microfluidic flow rate was varied, changes in Py aggregation states were influenced by a combination of Py core concentrations and Py interfacial localization. The techniques demonstrated here provide a general template for evaluating how manufacturing conditions influence molecular-scale features of vital importance to the efficacy of drug delivery nanoparticles.