Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties
Date
2019
Authors
Cao, Yimeng
Silverman, Lisa
Lu, Changhai
Hof, Rebecca
Wulff, Jeremy E.
Moffitt, Matthew G.
Journal Title
Journal ISSN
Volume Title
Publisher
Molecular Pharmaceutics
Abstract
Two-phase gas–liquid microfluidic reactors provide shear processing control of SN-38-loaded polymer nanoparticles (SN-38-PNPs). We prepare SN-38-PNPs from the block copolymer poly(methyl caprolactone-co-caprolactone)-block-poly(ethylene oxides) (P(MCL-co-CL)-b-PEO) using bulk and microfluidic methods and at different drug-to-polymer loading ratios and on-chip flow rates. We show that, as the microfluidic flow rate (Q) increases, encapsulation efficiency and drug loading increase and release half times increase. Slower SN-38 release is obtained at the highest Q value (Q = 400 μL/min) than is achieved using a conventional bulk preparation method. For all SN-38-PNP formulations, we find a dominant population (by number) of nanosized particles (<50 nm) along with a small number of larger aggregates (>100 nm). As Q increases, the size of aggregates decreases through a minimum and then increases, attributed to a flow-variable competition of shear-induced particle breakup and shear-induced particle coalescence. IC25 and IC50 values of the various SN-38-PNPs against MCF-7 cells show strong flow rate dependencies that mirror trends in particle size. SN-38-PNPs manufactured on-chip at intermediate flow rates show both minimum particle sizes and maximum potencies with a significantly lower IC25 value than the bulk-prepared sample. Compared to conventional bulk methods, microfluidic shear processing in two-phase reactors provides controlled manufacturing routes for optimizing and improving the properties of SN-38 nanomedicines.
Description
Keywords
drug delivery, microfluidics, polymer nanoparticles, SN-38
Citation
Cao, Y., Silverman, L., Lu, C., Hof, R., Wulff, J. E., & Moffitt, M. G. (2019). Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties. Molecular Pharmaceutics, 16(1), 96-107. https://doi.org/10.1021/acs.molpharmaceut.8b00874.