title: A platform for predicting and enhancing model drug delivery across the human nail plate.
abstract: OBJECTIVE
  The objective of the present study was to assess the effect of pretreatment using chemical etchants on the delivery of terbinafine hydrochloride (TH) and 5-fluorouracil (5-FU) into and across the human nail plate.
  
  
  METHODS
  The TranScreen-N method was used to screen five potential etchants. Based on these results, the dorsal surface of nails was pretreated with chemical etchants, 1% or 10% (w/w) phosphoric acid (PA) or 10% (w/w) lactic acid (LA) gels, for a period of 60 seconds. The nail pretreated with a plain gel formulation (no PA or LA incorporated) was used as the control.
  
  
  RESULTS
  Despite the differences in physicochemical properties between TH (log P = 3.3) and 5-FU (log P = -0.83), the in vitro permeation as well as drug load of these drugs in the nail plate was enhanced because of pretreatment with the PA gels, whereas LA pretreatment failed to enhance the drug load and permeation. Optical microscopic and atomic force microscopy studies revealed that the PA enhanced the trans-ungual drug delivery by decreasing the keratin density of the dorsal layer of the nail plate and by microstructural alterations.
  
  
  CONCLUSIONS
  This study demonstrated that pretreatment of the nail plate with PA (1% or 10%, w/w) for a short duration could be a potential method of improving the efficiency of topical monotherapy treatment for nail diseases.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of Mississippi, University, MS, USA.
authors.forename: Siva Ram Kiran
authors.initials: SR
authors.lastname: Vaka
authors.forename: Satyanarayana Narasimha
authors.initials: SN
authors.lastname: Murthy
authors.forename: John H
authors.initials: JH
authors.lastname: O'Haver
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D000287:Administration, Topical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D009260:Nail Diseases / Q000188:drug therapy / Q000378:metabolism; D009262:Nails / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D010756:Phosphoric Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D000077291:Terbinafine
chemical_list: D005782:Gels; D009281:Naphthalenes; D010756:Phosphoric Acids; C030242:phosphoric acid; D000077291:Terbinafine; D005472:Fluorouracil