title: Ciclopirox delivery into the human nail plate using novel lipid diffusion enhancers.
abstract: BACKGROUND
  Onychomycosis is a common fungal infection of the nail plate and bed that affects up to 14% of the population and can have a substantial impact on the quality of life of those affected.
  
  
  OBJECTIVE
  This study compared the onychopharmacokinetics, nail absorption, nail distribution, and nail penetration of [(14)C]-ciclopirox dissolved in novel lipid diffusion enhancers with that of a commercial ciclopirox nail lacquer using the in vitro finite dose model.
  
  
  METHODS
  The penetration rate of ciclopirox was determined by applying doses of topical formulation twice daily to human nail plates for 11 d. Drug absorption was then measured by monitoring its rate of appearance in each nail layer and in the cotton pad/nail supporting bed.
  
  
  RESULTS
  After a multiple day treatment, cumulative concentrations of ciclopirox formulated with lipid enhancers in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of the commercial ciclopirox lacquer (p < 0.001) as well as several orders of magnitude greater than the minimal inhibitory concentration (MIC) deemed necessary to inhibit the growth of the causative dermatophyte species.
  
  
  CONCLUSIONS
  When formulated with lipid enhancers, the amount of ciclopirox in the ventral/intermediate layer and supporting bed dramatically exceed the inhibitory concentration of ciclopirox for the most common onychomycosis organisms. These results suggest that topical ciclopirox with lipid enhancers has the potential to be an effective topical treatment for onychomycosis, and the lipidic pathway of the nail can be utilized as a means of effective transungual delivery.
authors.affiliation: Dermatology Department, University of California , San Francisco, CA , USA and.
authors.forename: Farhaan
authors.initials: F
authors.lastname: Hafeez
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Hui
authors.forename: Marc
authors.initials: M
authors.lastname: Selner
authors.forename: Bert
authors.initials: B
authors.lastname: Rosenthal
authors.forename: Howard
authors.initials: H
authors.lastname: Maibach
mesh_terms: D065966:Absorption, Physicochemical; D000287:Administration, Topical; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002102:Cadaver; D000077768:Ciclopirox; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D009262:Nails / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014009:Onychomycosis / Q000188:drug therapy / Q000378:metabolism; D010539:Permeability; D011728:Pyridones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008055:Lipids; D011728:Pyridones; D000077768:Ciclopirox
keywords: Ciclopirox; MIC, onychomycosis; human nail; in vitro; onychopharmacokinetics; topical formulation