Controlling Structure and Function of Polymeric Drug Delivery Nanoparticles Using Microfluidics.

We demonstrate control of multiscale structure and drug delivery function for paclitaxel (PAX)-loaded polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) polymeric nanoparticles (PNPs) via synthesis and flow-directed shear processing in a two-phase gas-liquid microfluidic reactor. This strategy takes a page from the engineering of commodity plastics, where processing rather than polymer chemistry provides an experimental handle on properties and function. PNPs formed from copolymers with three different PCL block lengths show sizes, morphologies, and loading efficiencies that depend on both the PCL block length and the microfluidic flow rate. By varying flow rate and comparing with a conventional bulk method of PNP preparation, we show that flow-variable shear processing provides control of PNP sizes and morphologies and enables slower PAX release times (up to 2 weeks) compared to bulk-prepared PNPs. Antiproliferative effects against cultured MCF-7 breast cancer cells were greatest for PNPs formed at an intermediate flow rate, corresponding to small and low-polydispersity spheres formed uniquely at this flow condition. Formation and flow-directed nanoscale shear processing in gas-liquid microfluidic reactors provides a manufacturing platform for drug delivery PNPs that could enable more effective and selective nanomedicines through multiscale structural control.