Pharmaceutical Research

, 36:11 | Cite as

New Classes of Polycationic Compounds as Preservatives for Ophthalmic Formulations

  • Dörte von Deylen
  • Christina Dreher
  • Oliver Seidelmann
  • Stephan ReichlEmail author
Research Paper
Part of the following topical collections:
  1. Ophthalmic Drug Discovery and Development



The purpose of this research work was to develop new polycationic compounds based on pyridine and piperidine structures with high antimicrobial activities against bacteria and fungi. Furthermore, the compounds should offer a lower toxicity than the commonly used preservatives for ophthalmic formulations, such as benzalkonium chloride (BAC) and polyquaternium-1 (PQ1).


Two polymers and three dimeric compounds were developed. Minimum inhibitory concentrations were determined for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus brasiliensis. The compounds were characterized regarding their impact on cell viability, cytotoxicity, epithelial integrity and surface tension. MTT and CytoTox-Glo™ assays, permeation studies with mannitol and transepithelial electrical resistance (TEER) measurements were performed on human corneal epithelial or MDCK I cells. BAC and PQ1 were used as references.


Three polycationic compounds exhibited high antimicrobial activity against the tested microorganisms comparable to that of BAC. Four compounds were tolerated as well as or better than PQ1. In addition, the TEER, permeability and surface tension were only affected by compounds with amphiphilic properties.


The pyridine- and piperidine-based polycationic compounds are promising candidates as new preservatives for ophthalmic formulations. Their high antimicrobial efficacy and good tolerability indicate a different mechanism of action compared to BAC.


benzalkonium chloride polycationic polymers polyquaternium-1 PQ1 preservatives ophthalmics 



Benzalkonium chloride


Colony forming unit


Dimer with dipyridine motif


Dimer with dipyridine motif and C10 alkyl chain in the end group


Dimer with dipyridine motif and C12 alkyl chain in the end group


Gel permeation chromatography


Human corneal epithelial cells


Krebs-Ringer buffer

log P

logarithmic partition coefficient


Madin-Darby canine kidney cells


Mueller-Hinton broth


Minimum inhibitory concentration


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Potato dextrose agar


Polymer with dipiperidine motif


Polymer with dipyridine motif




Sabouraud dextrose agar


Standard deviation


Transepithelial electrical resistance


Tryptic soy agar


Tryptic soy broth

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Dörte von Deylen
    • 1
  • Christina Dreher
    • 2
  • Oliver Seidelmann
    • 2
  • Stephan Reichl
    • 1
    Email author
  1. 1.Institut für Pharmazeutische TechnologieTechnische Universität BraunschweigBraunschweigGermany
  2. 2.ChiroBlock GmbHWolfenGermany

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