RRC ID 54722
Author von Deylen D, Dreher C, Seidelmann O, Reichl S.
Title New Classes of Polycationic Compounds as Preservatives for Ophthalmic Formulations.
Journal Pharm. Res.
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.
Volume 36(1)
Pages 11
Published 2018-11-8
DOI 10.1007/s11095-018-2536-9
PII 10.1007/s11095-018-2536-9
PMID 30411196
MeSH Administration, Ophthalmic Anti-Infective Agents* / administration & dosage Anti-Infective Agents* / chemistry Benzalkonium Compounds / administration & dosage Benzalkonium Compounds / chemical synthesis Benzalkonium Compounds / therapeutic use Cell Line Drug Compounding Epithelial Cells / drug effects Humans Microbial Sensitivity Tests Ophthalmic Solutions* / administration & dosage Ophthalmic Solutions* / chemistry Polyamines* Polymers / administration & dosage Polymers / chemical synthesis Polymers / therapeutic use Preservatives, Pharmaceutical* / administration & dosage Preservatives, Pharmaceutical* / chemistry Pseudomonas aeruginosa / drug effects
IF 3.335
Human and Animal Cells HCE-T(RCB2280)