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Open AccessArticle

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
2
Oncode Institute, 3553 Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(11), 590; https://doi.org/10.3390/pharmaceutics11110590
Received: 30 September 2019 / Revised: 3 November 2019 / Accepted: 6 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines. View Full-Text
Keywords: PLGA; drug delivery systems; microfluidics; nanoparticles; microparticles PLGA; drug delivery systems; microfluidics; nanoparticles; microparticles
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Operti, M.C.; Dölen, Y.; Keulen, J.; van Dinther, E.A.W.; Figdor, C.G.; Tagit, O. Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles. Pharmaceutics 2019, 11, 590.

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