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New Classes of Polycationic Compounds as Preservatives for Ophthalmic Formulations.
- Source :
-
Pharmaceutical research [Pharm Res] 2018 Nov 08; Vol. 36 (1), pp. 11. Date of Electronic Publication: 2018 Nov 08. - Publication Year :
- 2018
-
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).<br />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.<br />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.<br />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.
- Subjects :
- Administration, Ophthalmic
Benzalkonium Compounds administration & dosage
Benzalkonium Compounds chemical synthesis
Benzalkonium Compounds therapeutic use
Cell Line
Drug Compounding
Epithelial Cells drug effects
Humans
Microbial Sensitivity Tests
Polyelectrolytes
Polymers administration & dosage
Polymers chemical synthesis
Polymers therapeutic use
Pseudomonas aeruginosa drug effects
Anti-Infective Agents administration & dosage
Anti-Infective Agents chemistry
Ophthalmic Solutions administration & dosage
Ophthalmic Solutions chemistry
Polyamines
Preservatives, Pharmaceutical administration & dosage
Preservatives, Pharmaceutical chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 30411196
- Full Text :
- https://doi.org/10.1007/s11095-018-2536-9