Polymeric Nanocarrier Formulations of Biologics Using Inverse Flash NanoPrecipitation

Chester E. Markwalter, Robert F. Pagels, Ava N. Hejazi, Akiva G.R. Gordon, Alexandra L. Thompson, Robert K. Prud’homme

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The encapsulation of water-soluble therapeutics and biologics into nanocarriers to produce novel therapeutics has been envisioned for decades, but clinical translation has been hampered by complex synthesis strategies. The methods that have been developed are often limited by poor encapsulation efficiency/loading or complex processing to achieve therapeutic loadings high enough to be medically relevant. To address this unmet need, we introduce a solubility-driven self-assembly process to form polymeric nanocarriers comprising a biologic in a hydrophilic core, encapsulated by a poly(lactic acid) shell, and stabilized by a poly(ethylene glycol) brush. Called “inverse Flash NanoPrecipitation (iFNP),” the technique achieves biologic loadings (wt% of total formulation) that are 5–15× higher than typical values (9–27% versus < 2%). In contrast to liposomes and polymersomes, we sequentially assemble the polymer layers to form the final nanocarrier. Installation of the poly(lactic acid) shell before water exposure sequesters the biologic in the core and results in the improved loadings that are achieved. We demonstrate the broad applicability of the process and illustrate its implementation by formulating over a dozen different oligosaccharides, antibiotics, peptides, proteins, and RNA into nanocarriers with narrow size distributions, at high loadings, and with high reproducibility. Lysozyme and horseradish peroxidase are shown to retain 99% activity after processing. These results demonstrate the potential for commercial implementation of this technology, enabling the translation of novel treatments in immunology, oncology, or enzyme therapies.

Original languageEnglish (US)
Article number18
JournalAAPS Journal
Issue number2
StatePublished - Mar 1 2020

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


  • Drug Delivery
  • FNP
  • Nanocarrier
  • Nanoparticle
  • Peptide
  • Protein


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