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Licensed Unlicensed Requires Authentication Published by De Gruyter June 3, 2016

Nano-mupirocin: enabling the parenteral activity of mupirocin

Ahuva Cern, Ayelet Michael-Gayego, Yaelle Bavli, Erez Koren, Amiram Goldblum, Allon E. Moses, Yan Q. Xiong and Yechezkel Barenholz


Mupirocin is an antibiotic having a unique mode of action, not shared by any other therapeutically available antibiotic. However, due to its rapid elimination following injection and high protein binding, current therapeutic use is limited to topical administration. Computational methods have identified mupirocin as a good candidate for delivery via long-circulating nano-liposomes. Formulating mupirocin in such liposomes to form Nano-mupirocin protects the drug in the circulation, enabling therapeutic efficacy. This was demonstrated using two different animal models that served as a proof of concept: the mice necrotizing fasciitis and rabbit endocarditis models. In both animal models, mupirocin administered intravenously (IV) lacked therapeutic efficacy, while the Nano-mupirocin administered IV was efficacious. In both mice and rabbits the pharmacokinetic (PK) profile following IV injection of Nano-mupirocin showed significantly greater AUC and elimination half-life of Nano-mupirocin compared to the free drug. In addition, in mice we also demonstrated significant drug distribution into the disease site. These PK profiles may explain Nano-mupirocin’s superior therapeutic efficacy. To the best of our knowledge, this is the first study demonstrating that systemic activity of mupirocin is feasible. Therefore, Nano-mupirocin can be considered a novel and unique parenteral antibiotic candidate drug.


This study was supported by Kamin grant of The Chief Scientist at the Israeli Ministry of Economy and by the Barenholz Fund at the Hebrew University of Jerusalem. This fund originated from royalties Hebrew University received from Yechezkel Barenholz’s commercialized projects. Part of this money is used to support the research activities of the Barenholz Lab. We authors would like to acknowledge Dr. Mary Dan-Goor for her help with the mice study. Mr. Sioma Nudelman and Mrs. Olga Gutman for their help in the preparation of Nano-mupirocin and Mr. Sigmund Geller for editing this paper.

  1. Conflict of interest statement: Y. Barenholz, A. Goldblum and A. Cern are co-inventors on a patent application owned by Yissum, the TTO of the Hebrew University of Jerusalem, that was not yet commercialized.


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Received: 2016-3-16
Accepted: 2016-4-27
Published Online: 2016-6-3
Published in Print: 2016-7-1

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