title: Nanoparticle-mediated delivery of the antimicrobial peptide plectasin against Staphylococcus aureus in infected epithelial cells.
abstract: A number of pathogenic bacterial strains, such as Staphylococcus aureus, are difficult to kill with conventional antibiotics due to intracellular persistence in host airway epithelium. Designing drug delivery systems to deliver potent antimicrobial peptides (AMPs) intracellularly to the airway epithelial cells might thus be a promising approach to combat such infections. In this work, plectasin, which is a cationic AMP of the defensin class, was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles using the double emulsion solvent evaporation method. The nanoparticles displayed a high plectasin encapsulation efficiency (71-90%) and mediated release of the peptide over 24h. The antimicrobial efficacy of the peptide-loaded nanoparticles was investigated using bronchial epithelial Calu-3 cell monolayers infected with S. aureus. The plectasin-loaded nanoparticles displayed improved efficacy as compared to non-encapsulated plectasin, while the eukaryotic cell viability was unaffected at the assayed concentrations. Further, the subcellular localization of the nanoparticles was assessed in different relevant cell lines. The nanoparticles were distributed in punctuate patterns intracellularly in Calu-3 epithelial cells and in THP-1 macrophages, whereas A549 epithelial cells did not show significant uptake of the nanoparticles. Overall, encapsulation of plectasin into PLGA-based nanoparticles appears to be a viable strategy to improve the efficacy of plectasin against infections in epithelial tissues.
authors.affiliation: Section for Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jorrit Jeroen
authors.initials: JJ
authors.lastname: Water
authors.affiliation: Section for Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pharmacy and Pharmacology, Faculty of Science, University of Bath, Bath, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Smart
authors.affiliation: Section for Natural Products Research, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Franzyk
authors.affiliation: Section for Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Foged
authors.affiliation: Section for Biologics, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: hanne.morck@sund.ku.dk.
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008264:Macrophages; D053758:Nanoparticles; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012997:Solvents / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D004655:Emulsions; D010455:Peptides; D012997:Solvents; C504857:plectasin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: A549; Antibiotics; Antimicrobial peptide; Calu-3; Infected epithelial cells; PLGA; Polymeric nanoparticles; Pulmonary drug delivery; Staphylococcus aureus; THP-1