Flash nanoprecipitation for the encapsulation of hydrophobic and hydrophilic compounds in polymeric nanoparticles

Chester E. Markwalter, Robert F. Pagels, Brian K. Wilson, Kurt D. Ristroph, Robert K. Prud’homme

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can improve bioavailability and modify drug distribution within the body. For hydrophilic drugs like peptides or proteins, encapsulation within NPs can also provide protection from natural clearance mechanisms. There are few techniques for the production of polymeric NPs that are scalable. Flash NanoPrecipitation (FNP) is a process that uses engineered mixing geometries to produce NPs with narrow size distributions and tunable sizes between 30 and 400 nm. This protocol provides instructions on the laboratory-scale production of core-shell polymeric nanoparticles of a target size using FNP. The protocol can be implemented to encapsulate either hydrophilic or hydrophobic compounds with only minor modifications. The technique can be readily employed in the laboratory at milligram scale to screen formulations. Lead hits can directly be scaled up to gram- and kilogram-scale. As a continuous process, scale-up involves longer mixing process run time rather than translation to new process vessels. NPs produced by FNP are highly loaded with therapeutic, feature a dense stabilizing polymer brush, and have a size reproducibility of ± 6%.

Original languageEnglish (US)
Article numbere58757
JournalJournal of Visualized Experiments
Issue number143
StatePublished - Jan 2019

All Science Journal Classification (ASJC) codes

  • General Chemical Engineering
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


  • Bioengineering
  • Block copolymer
  • Drug delivery
  • Issue 143
  • Micromixing
  • Nanoparticle
  • Peptide
  • Process scale-up
  • Protein


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