Intestinal Transcytosis of a Protein Cargo and Nanoparticles Mediated by a Non-toxic Form of Pseudomonas aeruginosa exotoxin A

Molly (Ruiying) Li, Floriane Laurent, Alistair Taverner, Julia Mackay, Paul De Bank, Randy Mrsny

Research output: Contribution to journalArticlepeer-review

Abstract

The low permeability of nanoparticles (NPs) across the intestinal epithelium remains a major challenge for their application of delivering macromolecular therapeutic agents via the oral route. Previous studies have demonstrated the epithelial transcytosis capacity of a non-toxic version of Pseudomonas aeruginosa exotoxin A (ntPE). Here, we show that ntPE can be used to deliver the protein cargo red fluorescent protein (GFP) or human growth hormone (hGH), as genetic fusions, across intact rat jejunum in a model where the material is administered by direct intra-luminal injection (ILI) in vivo in a transcytosis process that required less than 15 min. Next, ntPE chemically coupled onto biodegradable alginate/chitosan condensate nanoparticles (AC NPs-ntPE) were shown to transport similarly to ntPE-GFP and ntPE-hGH across rat jejunum. Finally, AC NPs-ntPE loaded with GFP as a model cargo, were demonstrated to undergo a similar transcytosis process that resulted in GFP being colocalized with CD11c+ cells in the lamina propria after 30 minutes. Control NP preparations, not decorated with ntPE, were not observed within polarized epithelial cells or within cells of the lamina propria. These studies demonstrate the capacity of ntPE to facilitate transcytosis of a covalently associated protein cargo as well as a biodegradable NP that can undergo transcytosis across the intestinal epithelium to deliver a noncovalently associated protein cargo. In sum, these studies support potential applications of ntPE to facilitate the oral delivery of macromolecular therapeutics under conditions of covalent or non-covalent association.
Original languageEnglish
Article number1171
JournalPharmaceutics
Volume13
Issue number8
Publication statusPublished - 29 Jul 2021

Keywords

  • Oral protein delivery
  • in vivo model
  • transcytosis
  • nanoparticle

ASJC Scopus subject areas

  • Pharmaceutical Science

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