A Versatile, Low-Cost Modular Microfluidic System to Prepare Poly(Lactic-co-Glycolic Acid) Nanoparticles With Encapsulated Protein

Pharmaceutical Research, vol. 41, pp. 2347–2361

Abstract

OBJECTIVE: Microfluidics has emerged as a promising technique to prepare nanoparticles. However, the current microfluidic devices are mainly chip-based and are often integrated into expensive systems that lack on-the-spot versatility. The aim of this study was to set up a modular microfluidic system based on low-cost capillaries and reusable, easy-to-clean building blocks that can prepare poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with and without incorporated water-soluble biomacromolecules. METHODS: A two-syringe system variant of the microfluidic system was set up to prepare PLGA particles and to investigate how the flow rates, solvents, and PLGA concentrations impacted the PLGA nanoparticle formation. A three-syringe system was designed to examine the incorporation of proteins into the PLGA particles. RESULTS: The formation of the nanoparticles was affected by the PLGA concentration in the organic solvent, where an increasing concentration led to larger particle diameters (33-180 nm), and by the total flow rate, where an increase in the total flow rate led to smaller nanoparticles (197-77 nm). Using ultrapure water as the aqueous solvent resulted in precipitation at the outlet at higher PLGA concentrations. Aqueous poly(vinyl alcohol) created neutral particles in contrast to the negatively charged particles obtained with ultrapure water or an ethanol-water mixture. Incorporation of the proteins ovalbumin or lysozyme with a three-syringe system resulted in encapsulation efficiencies above 40%. CONCLUSION: A cheap and easily adjustable modular microfluidic system was developed to prepare PLGA nanoparticles with highly reproducible particle diameters that can effectively be loaded with proteins for drug and vaccine delivery.

Authors 5

1. Malene Aaby Neustrup Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

2. Tom H. M. Ottenhoff Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands

3. Wim Jiskoot Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands

4. Joke A. Bouwstra Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands

5. Koen van der Maaden corresponding Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research Tumor Immunology Group Department of Immunology, Leiden University Medical Center

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. k.van_der_maaden@lumc.nl

   Tumor Immunology Group, Department of Immunology, Leiden University Medical Center, Albinusdreef 2, Room E-03-030, 2300CC, Leiden, The Netherlands. k.van_der_maaden@lumc.nl