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Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)

Please always quote using this URN: urn:nbn:de:bvb:20-opus-148162
  • 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 forBackground 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.show moreshow less

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Author: Rebuma Firdessa, Liam Good, Maria Cecilia Amstalden, Kantaraja Chindera, Nor Fadhilah Kamaruzzaman, Martina Schultheis, Bianca Röger, Nina Hecht, Tobias A. Oelschlaeger, Lorenz Meinel, Tessa Lühmann, Heidrun Moll
URN:urn:nbn:de:bvb:20-opus-148162
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Language:English
Parent Title (English):PLoS Neglected Tropical Diseases
Year of Completion:2015
Volume:9
Issue:10
Pagenumber:e0004041
Source:PLoS Neglected Tropical Diseases 9(10): e0004041. DOI: 10.1371/journal. pntd.0004041
DOI:https://doi.org/10.1371/journal.pntd.0004041
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Cutaneous leishmaniasis; activation; biocide polyhexamethylene biguanide; dendritic cells; drug-delivery systems; experimental visceral leishmaniasis; paromomycin; resistance; therapy; topical treatment
Release Date:2018/11/08
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International