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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

Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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.

KEY WORDS

benzalkonium chloride polycationic polymers polyquaternium-1 PQ1 preservatives ophthalmics 

ABBREVIATIONS

BAC

Benzalkonium chloride

cfu

Colony forming unit

DiPy

Dimer with dipyridine motif

DiPyC10

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

DiPyC12

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

GPC

Gel permeation chromatography

HCE-T

Human corneal epithelial cells

KRB

Krebs-Ringer buffer

log P

logarithmic partition coefficient

MDCK I

Madin-Darby canine kidney cells

MHB

Mueller-Hinton broth

MIC

Minimum inhibitory concentration

MTT

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

PDA

Potato dextrose agar

PolyPi

Polymer with dipiperidine motif

PolyPy

Polymer with dipyridine motif

PQ1

Polyquaternium-1

SDA

Sabouraud dextrose agar

SD

Standard deviation

TEER

Transepithelial electrical resistance

TSA

Tryptic soy agar

TSB

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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