Control of structure and function of block copolymer nanoparticles manufactured in microfluidic reactors: towards drug delivery applications




Xu, Zheqi

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This thesis includes three studies on related aspects of structure and function control for drug delivery block copolymer nanoparticles manufactured in segmented gas-liquid microfluidic reactors. First, the self-assembly of a series of photoresponsive poly(o-nitrobenzyl acrylate)-b-polydimethylacrylamide copolymers is conducted in the gas-liquid segmented microfluidic reactor at various flow rates. The resulting morphologies are found to be flow-variable and distinct from nanoparticles prepared off-chip by dropwise water addition. Photocleaving of the nanoparticles formed at different flow rates reveal flow-variable photodissociation kinetics. Next, we conduct a direct comparison between a commercially-available single-phase microfluidic mixer and the two-phase, gas-liquid segmented microfluidic reactor used in our group, with respect to nanoparticle formation from a typical block copolymer identified for drug delivery applications, polycaprolactone-b-poly(ethylene oxide). The two-phase chip yields morphologies and core crystallinities that vary with flow rate; however, the same parameters are found to be flow-independent using the single-phase mixer. This study provides the first direct evidence that flow-variable structure control is a unique feature of the two-phase chip design. Finally, we investigate structure and function control for paclitaxel (PAX)-loaded nanoparticles prepared from a series of poly(6-methyl caprolactone-co-ε-caprolactone)-block-poly(ethylene oxide) copolymers with variable 6-methyl caprolactone (MCL) content. For all MCL-containing copolymers, off-chip preparations form nanoparticles with no measurable crystallinity, although PAX loading levels are higher and release rates are slower compared to the copolymer without MCL. Both off-chip and on-chip preparations yield amorphous spheres of similar size from MCL-containing copolymers, although on-chip nanoparticles showed slower release rates, attributed to more homogeneous PAX distribution due to faster mixing.



Microfluidics, Drug Delivery, Block Copolymer, Nanoparticles