Production and Evaluation of an Antimicrobial Peptide-Containing Wafer Formulation for Topical Application
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Production and Evaluation of an Antimicrobial Peptide-Containing Wafer Formulation for Topical Application Noelle H. O’Driscoll • Olga Labovitiadi • T. P. Tim Cushnie • Kerr H. Matthews • Derry K. Mercer • Andrew J. Lamb
Received: 29 June 2012 / Accepted: 12 November 2012 / Published online: 25 November 2012 Ó Springer Science+Business Media New York 2012
Abstract A targeted approach for direct topical antimicrobial delivery involving the formulation of impregnated freeze-dried wafers prepared from a natural polymer has been assessed to consider potential for treatment of wounded skin. The synthetic cationic antimicrobial peptides (CAPs) NP101 and NP108 were found to have modest in vitro activity against bacterial species commonly associated with wound infections. Minimum inhibitory concentration/minimum bactericidal concentrations against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were found
to be 0.31 mg/ml for NP101 and 0.25–0.5 mg/ml for NP108. Rapid, substantial cytoplasmic potassium loss was induced by NP108 in E. coli, but not the other species. Through scanning electron microscopy, both CAPs were observed to alter cell morphology, prevent normal septation, promote cell aggregation and trigger release or formation of extracellular filaments. Wafers harbouring these agents displayed substantial antibacterial activity when assessed by standard diffusion assay. These data confirm that topical delivery of CAPs, through their incorporation within freeze-dried wafer formulations prepared from natural polymers, represents a potential viable approach for treating skin infection.
Electronic supplementary material The online version of this article (doi:10.1007/s00284-012-0268-3) contains supplementary material, which is available to authorized users.
Introduction N. H. O’Driscoll K. H. Matthews A. J. Lamb (&) School of Pharmacy and Life Sciences, Research Institute for Health and Welfare, Robert Gordon University, Schoolhill, Aberdeen AB10 1FR, UK e-mail: [email protected] N. H. O’Driscoll e-mail: [email protected] K. H. Matthews e-mail: [email protected] O. Labovitiadi School of Science, University of Greenwich, Medway Campus, Chatham Maritime ME4 4AW, UK e-mail: [email protected] T. P. Tim Cushnie Faculty of Medicine, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham 44150, Thailand e-mail: [email protected] D. K. Mercer NovaBiotics Ltd., Cruickshank Building, Craibstone, Aberdeen AB21 9TR, UK e-mail: [email protected]
The inexorable rise in bacterial resistance to currently available antimicrobials has become a major cause for concern. For example, methicillin-resistant Staphylococcus aureus is now widespread in community as well as hospital settings, despite ongoing efforts to limit this spread [1–3]. New therapeutic agents and innovative methods for treating bacterial infections are urgently required, with cationic antimicrobial peptides (CAPs) being investigated as new therapeutic options [4]. CAPs have been shown to be effective against Gr
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