Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria
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 PEGylate...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2186 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ahuva Cern |
| collection | DOAJ |
| description | 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 methicillin- resistant <i>Staphylococcus aureus</i>, against vancomycin-resistant <i>Enterococcus faecium</i>, and cephalosporin-resistant <i>Neisseria gonorrhoeae</i>. 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 MIC<sub>90</sub> for <i>N. gonorrhoeae</i> (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<sup>®</sup>, an anticancer drug product now used for the treatment of over 700,000 patients globally. |
| first_indexed | 2024-03-10T03:19:34Z |
| format | Article |
| id | doaj.art-88f8dd726fd14c7a8535af5349bf0ad5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:34Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-88f8dd726fd14c7a8535af5349bf0ad52023-11-23T10:07:05ZengMDPI AGPharmaceutics1999-49232021-12-011312218610.3390/pharmaceutics13122186Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant BacteriaAhuva Cern0Yaelle Bavli1Atara Hod2Daniel Zilbersheid3Shazad Mushtaq4Ayelet Michael-Gayego5Dinorah Barasch6Yael Feinstein Rotkopf7Allon E. Moses8David M. Livermore9Yechezkel Barenholz10Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelLaboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelLaboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelLaboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelAntimicrobial Resistance and Healthcare-Associated Infections Reference Unit, UK Health Security Agency, London NW9 5HT, UKDepartment of Clinical Microbiology & Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem 9112102, IsraelThe Mass Spectrometry Unit, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelLight Microscopy Laboratory, Core Research Facility, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelDepartment of Clinical Microbiology & Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem 9112102, IsraelNorwich Medical School, University of East Anglia, Norwich NR4 7TJ, UKLaboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelAntibiotic 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 methicillin- resistant <i>Staphylococcus aureus</i>, against vancomycin-resistant <i>Enterococcus faecium</i>, and cephalosporin-resistant <i>Neisseria gonorrhoeae</i>. 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 MIC<sub>90</sub> for <i>N. gonorrhoeae</i> (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<sup>®</sup>, an anticancer drug product now used for the treatment of over 700,000 patients globally.https://www.mdpi.com/1999-4923/13/12/2186nano-liposomesmupirocinmulti-drug resistant bacteriainjectionpharmacokineticscross resistance |
| spellingShingle | 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 Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria Pharmaceutics nano-liposomes mupirocin multi-drug resistant bacteria injection pharmacokinetics cross resistance |
| title | Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria |
| title_full | Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria |
| title_fullStr | Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria |
| title_full_unstemmed | Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria |
| title_short | Therapeutic Potential of Injectable Nano-Mupirocin Liposomes for Infections Involving Multidrug-Resistant Bacteria |
| title_sort | therapeutic potential of injectable nano mupirocin liposomes for infections involving multidrug resistant bacteria |
| topic | nano-liposomes mupirocin multi-drug resistant bacteria injection pharmacokinetics cross resistance |
| url | https://www.mdpi.com/1999-4923/13/12/2186 |
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