title: In vitro antimycotic activity and nail permeation models of a piroctone olamine (octopirox) containing transungual water soluble technology.
abstract: Several in vitro studies with a new medical device (Myfungar) containing 0.5% of piroctone olamine (CAS 68890-66-4, octopirox) in a hydroxypropyl chitosan hydroalcoholic solution were performed. The chemical name of the active ingredient is 1-hydroxy-4-methyl-6 (2,4,4-trimethylpentyl)-2(1H)-pyridone; combination with 2-amino-ethanol (1:1). The antimycotic activity was determined in the most common fungi responsible of nail infections such as Candida parapsilosis, Scopulariopsis brevicaulis or Trichophyton rubrum. The minimum inhibitory concentration (MIC), found by means of the broth dilution susceptibility method, ranged between 0.0003% and 0.006% for all pathogens considered. The in vitro permeation study was performed by using bovine hoof membranes inserted in a modified Gummer vertical permeation cell. The experiment showed, at 30 h, a retention of the product in the nail membranes by 11.1% of the applied dose. No piroctone permeation through bovine hoof membranes could be detected by HPLC due to the limit of quantitation of this method. On the other hand, permeation of nail membranes has been demonstrated by a biological assay: the study of in vitro permeation through bovine hoof membranes, performed by biological assay, showed dose-dependent inhibition rings of T. rubrum growth by the tested device, placed either on disks for antibiogram or on nail fragments. The placebo did not show any inhibition. In vitro experimental infection by T. rubrum showed a preventive activity of the tested device on fungal growth as well as a curative activity, as the pathogen was eradicated by the tested solution in previously infected nails.
authors.affiliation: Institute of Microbiology, School of Medicine, University of Milan, Milan, Italy. francesco.dubini@unimi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Dubini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bellotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Frangi
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Luigi
authors.initials: L
authors.lastname: Saccomani
mesh_terms: D000818:Animals; D000935:Antifungal Agents; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D048271:Chitosan; D004338:Drug Combinations; D004864:Equipment and Supplies; D004983:Ethanolamines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006724:Hoof and Claw / Q000378:metabolism*; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D014009:Onychomycosis / Q000188:drug therapy / Q000382:microbiology; D010539:Permeability; D019999:Pharmaceutical Solutions; D011728:Pyridones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012995:Solubility; D014005:Tinea / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019999:Pharmaceutical Solutions; D011728:Pyridones; D048271:Chitosan; C052599:piroctone olamine