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Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)
BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Loc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592236/ https://www.ncbi.nlm.nih.gov/pubmed/26431058 http://dx.doi.org/10.1371/journal.pntd.0004041 |
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author | Firdessa, Rebuma Good, Liam Amstalden, Maria Cecilia Chindera, Kantaraja Kamaruzzaman, Nor Fadhilah Schultheis, Martina Röger, Bianca Hecht, Nina Oelschlaeger, Tobias A. Meinel, Lorenz Lühmann, Tessa Moll, Heidrun |
author_facet | Firdessa, Rebuma Good, Liam Amstalden, Maria Cecilia Chindera, Kantaraja Kamaruzzaman, Nor Fadhilah Schultheis, Martina Röger, Bianca Hecht, Nina Oelschlaeger, Tobias A. Meinel, Lorenz Lühmann, Tessa Moll, Heidrun |
author_sort | Firdessa, Rebuma |
collection | PubMed |
description | BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS: Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB’s DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS: Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators. |
format | Online Article Text |
id | pubmed-4592236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45922362015-10-09 Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) Firdessa, Rebuma Good, Liam Amstalden, Maria Cecilia Chindera, Kantaraja Kamaruzzaman, Nor Fadhilah Schultheis, Martina Röger, Bianca Hecht, Nina Oelschlaeger, Tobias A. Meinel, Lorenz Lühmann, Tessa Moll, Heidrun PLoS Negl Trop Dis Research Article BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS: Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB’s DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS: Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators. Public Library of Science 2015-10-02 /pmc/articles/PMC4592236/ /pubmed/26431058 http://dx.doi.org/10.1371/journal.pntd.0004041 Text en © 2015 Firdessa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Firdessa, Rebuma Good, Liam Amstalden, Maria Cecilia Chindera, Kantaraja Kamaruzzaman, Nor Fadhilah Schultheis, Martina Röger, Bianca Hecht, Nina Oelschlaeger, Tobias A. Meinel, Lorenz Lühmann, Tessa Moll, Heidrun Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title | Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title_full | Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title_fullStr | Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title_full_unstemmed | Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title_short | Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB) |
title_sort | pathogen- and host-directed antileishmanial effects mediated by polyhexanide (phmb) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592236/ https://www.ncbi.nlm.nih.gov/pubmed/26431058 http://dx.doi.org/10.1371/journal.pntd.0004041 |
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