Abstract 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.
European Journal of Nanomedicine – de Gruyter
Published: Jul 1, 2016
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