Therapeutic potential of injectable nano-mupirocin liposomes for infections involving multidrug-resistant bacteria

Ahuva Cern, Yaelle Bavli, Atara Hod, Daniel Zilbersheid, Shazad Mushtaq, Ayelet Michael-Gayego, Dinorah Barasch, Yael Feinstein Rotkopf, Allon E. Moses, David M. Livermore, Yechezkel Barenholz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Antibiotic resistance is a global health threat. There are a few antibiotics under development, and even fewer with new modes of action and no cross-resistance to established antibiotics. Accordingly, reformulation of old antibiotics to overcome resistance is attractive. Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin, potentially enabling parenteral use in deep infections, as previously demonstrated in several animal models. Here, we describe extensive in vitro profiling of mupirocin and Nano-mupirocin and correlate the resulting MIC data with the pharmacokinetic profiles seen for Nano-mupirocin in a rat model. Nano-mupirocin showed no cross-resistance with other antibiotics and retained full activity against vancomycin-, daptomycin-, linezolid-and methicillinresistant Staphylococcus aureus, against vancomycin-resistant Enterococcus faecium, and cephalosporinresistant Neisseria gonorrhoeae. Following Nano-mupirocin injection to rats, plasma levels greatly exceeded relevant MICs for >24 h, and a biodistribution study in mice showed that mupirocin concentrations in vaginal secretions greatly exceeded the MIC90 for N. gonorrhoeae (0.03 µg/mL) for >24 h. In summary, Nano-mupirocin has excellent potential for treatment of several infection types involving multiresistant bacteria. It has the concomitant benefits from utilizing an established antibiotic and liposomes of the same size and lipid composition as Doxil®, an anticancer drug product now used for the treatment of over 700,000 patients globally.

Original languageAmerican English
Article number2186
JournalPharmaceutics
Volume13
Issue number12
DOIs
StatePublished - 17 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cross resistance
  • Injection
  • Multi-drug resistant bacteria
  • Mupirocin
  • Nano-liposomes
  • Neisseria gonorrhoeae
  • Pharmacokinetics
  • Vaginal distribution
  • Vancomycin-resistant E. faecium

Fingerprint

Dive into the research topics of 'Therapeutic potential of injectable nano-mupirocin liposomes for infections involving multidrug-resistant bacteria'. Together they form a unique fingerprint.

Cite this