Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

PLoS Negl Trop Dis. 2015 Oct 2;9(10):e0004041. doi: 10.1371/journal.pntd.0004041. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biguanides / pharmacology*
  • Cells, Cultured
  • Female
  • Leishmania major / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / pharmacology


  • Biguanides
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • polihexanide

Grants and funding

RF was supported by fellowships of the German Excellence Initiative to the Graduate School of Life Sciences and DAAD STIBET Abschlussbeihilfe, University of Würzburg, Germany. MCA is supported by Science without Borders Program, CAPES Foundation, Ministry of Education of Brazil, Brasilia. We are grateful for support by the SFB 630 of the Deutsche Forschungsgemeinschaft (DFG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.