Development of an Arginine Anchored Nanoglobule with Retrograde Trafficking Inhibitor (Retro-2) for the Treatment of an Enterohemorrhagic Escherichia coli Outbreak

Tasneem Gandhi, Manali Patki, Jing Kong, Jagadish Koya, Sabesan Yoganathan, Sandra Reznik, Ketankumar Patel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Enterohemorrhagic Escherichia coli O157:H7 (EHEC) or Shiga toxin-producing E. coli (STEC) is known to cause sporadic and epidemic gastrointestinal infections with several incidences of outbreaks. Antibiotic-based therapy further worsens the condition by facilitating the release of Shiga toxins (Stx) and lipopolysaccharides (LPS). Hence, there is an urgent need to develop an antibiotic-free, safe, and effective therapeutic intervention for the treatment of EHEC infections. We proposed a novel therapeutic strategy to address this clinical problem - kill, capture, and inhibit. We aimed to formulate and characterize lauroyl arginate ethyl ester (LAE) and Retro-2 loaded self-nano emulsifying drug delivery systems (SNEDDS). Retro-2 is a recently developed novel class of molecule, which can selectively inhibit retrograde transport of Stx. In this paper, we first carried out preformulation studies of Retro-2, followed by the development of SNEDDS forming arginine anchored nanoglobules (AR-NG), characterization of LPS binding to AR-NG, and finally evaluation of activity against EHEC. Retro-2 showed extremely poor solubility at all gastrointestinal pH values, susceptibility to acidic environments, and good permeability. The positively charged AR-NG spontaneously formed a globule size of 102.8 ± 1.9 nm with a surface charge of +52.15 ± 3 mV and increased the solubility of Retro-2. Further, binding and aggregation of LPS and AR-NG were confirmed by particle size, polydispersity index, zeta potential, fluorescent intensity, turbidity analysis, and a limulus amebocyte lysate (LAL) test. Additionally, a significant reduction in LPS induced TNF-α was observed in AR-NG treated macrophages. Thus, in this paper, we demonstrate a very promising and innovative therapeutic approach based on the "kill (E. Coli), capture (released LPS), and inhibit (transport of Stx)" concept.

Original languageEnglish (US)
Pages (from-to)4405-4415
Number of pages11
JournalMolecular Pharmaceutics
Issue number10
StatePublished - Oct 7 2019
Externally publishedYes


  • EHEC
  • Retro-2
  • Shiga-like toxin
  • lipopolysaccharides

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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