New Classes of Polycationic Compounds as Preservatives for Ophthalmic Formulations
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.
KEY WORDSbenzalkonium chloride polycationic polymers polyquaternium-1 PQ1 preservatives ophthalmics
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
- log P
logarithmic partition coefficient
- MDCK I
Madin-Darby canine kidney cells
Minimum inhibitory concentration
Potato dextrose agar
Polymer with dipiperidine motif
Polymer with dipyridine motif
Sabouraud dextrose agar
Transepithelial electrical resistance
Tryptic soy agar
Tryptic soy broth
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