title: Development of a nose cream containing the synthetic antimicrobial peptide P60.4Ac for eradication of methicillin-resistant Staphylococcus aureus carriage.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing problem, and current treatment options are suboptimal. Nasal carriage of MRSA is a major risk factor for infection, but nasal eradication strategies are increasingly considered to be insufficiently effective. In this study, a water-in-oil cream formulation was developed for nasal application with an antimicrobial peptide, P60.4Ac, aimed at the eradication of MRSA carriage. Quality control of the cream included the measurement of the content and release of the peptide by a validated high-performance liquid chromatography method. Stability of the peptide in the formulation was investigated including the evaluation of the effect of stress conditions. Preliminary shelf-life study of the drug formulation demonstrated that the peptide is stable in the formulation at least for 5 months. Microbial-killing assays with MRSA LUH14616 as a target demonstrated the dose-dependent antimicrobial activity of the peptide formulation.
authors: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Anikó
authors: A
authors: Göblyös
authors: Kirsten J M
authors: KJ
authors: Schimmel
authors: A Rob P M
authors: AR
authors: Valentijn
authors: Lorainne M
authors: LM
authors: Fathers
authors: Robert A
authors: RA
authors: Cordfunke
authors: Hee Lam
authors: HL
authors: Chan
authors: Jaap
authors: J
authors: Oostendorp
authors: Peter H
authors: PH
authors: Nibbering
authors: Jan W
authors: JW
authors: Drijfhout
authors: Pieter S
authors: PS
authors: Hiemstra
authors: Jan Den
authors: JD
authors: Hartigh
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000890:Anti-Infective Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D009666:Nose / Q000187:drug effects* / Q000382:microbiology; D009821:Oils / Q000737:chemistry; D009824:Ointments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014867:Water / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D009821:Oils; D009824:Ointments; D010455:Peptides; D014867:Water
keywords: HPLC (high performance/pressure liquid chromatography) analysis, analysis; antimicrobial peptides; antimicrobial treatment; formulation; nose cream; peptides; solid-phase peptide synthesis; synthesis