title: Production and evaluation of an antimicrobial peptide-containing wafer formulation for topical application.
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.
authors.affiliation: School of Pharmacy and Life Sciences, Research Institute for Health and Welfare, Robert Gordon University, Schoolhill, Aberdeen, AB10 1FR, UK. n.o-driscoll@rgu.ac.uk
authors.forename: Noelle H
authors.initials: NH
authors.lastname: O'Driscoll
authors.forename: Olga
authors.initials: O
authors.lastname: Labovitiadi
authors.forename: T P Tim
authors.initials: TP
authors.lastname: Cushnie
authors.forename: Kerr H
authors.initials: KH
authors.lastname: Matthews
authors.forename: Derry K
authors.initials: DK
authors.lastname: Mercer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lamb
mesh_terms: D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005612:Freeze Drying; D008826:Microbial Sensitivity Tests; D011188:Potassium / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014946:Wound Infection / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011188:Potassium