Polymersomes scalably fabricated via flash nanoprecipitation are non-toxic in non-human primates and associate with leukocytes in the spleen and kidney following intravenous administration

Sean D. Allen, Yu Gang Liu, Sharan Bobbala, Lei Cai, Peter I. Hecker, Ryan Temel, Evan A. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles (polymersomes) have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS) polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/(kg·week). Following the administration of a more relevant 20 mg/(kg·week) dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and > 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bl-PPS polymersomes into the clinic for therapeutic applications in humans.

Original languageEnglish (US)
Pages (from-to)5689-5703
Number of pages15
JournalNano Research
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2018

Keywords

  • biodistribution
  • nanoprecipitation
  • non-human primate
  • polymersome
  • toxicity

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

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