A platform for predicting and enhancing model drug delivery across the human nail plate.

PURPOSE: 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.

Transcorneal iontophoresis for delivery of ciprofloxacin hydrochloride.

PURPOSE: To investigate the feasibility of utilizing iontophoresis for delivery of ciprofloxacin hydrochloride to the anterior chamber of the eye and to carry out systematic studies to investigate the effect of electrical protocol on the transcorneal drug delivery. MATERIALS AND METHODS: Effect of current density (0.75 mA/cm(2) to 6.25 mA/cm(2) applied for 5 minutes) on drug permeation across the cornea and drug load in the cornea were investigated in vitro as well as ex vivo studies in porcine cornea model. Tolerability studies were carried out in rabbits. Cytotoxicity studies were conducted in cultured corneal tissue. RESULTS: The drug loaded in the cornea increased with increasing current density. After 5 minutes of iontophoresis, the drug concentration in the receiver compartment fluid (in vitro) or in aqueous humor (ex vivo) was not significantly higher than control (in which electric current was not applied). However, waiting for 6-12 hours after iontophoresis for 5 minutes, the concentrations of drug in aqueous humor in ex vivo studies were approximately 6 and approximately 5-fold higher than control (130.12 +/- 78.99 ng/ml), respectively. Cytotoxicity studies demonstrated the safety of the technique. The application of 6.25 mA/cm(2) for 5 minutes (right eye) did not show any sign of loss of vision and abnormal discharge, redness of eye, or edema when compared to the control left eye. CONCLUSIONS: Transcorneal iontophoresis is a potential method of delivering effective levels of ciprofloxacin hydrochloride into aqueous humor for the treatment of intraocular infections. This study unveils the ability of iontophoresis to rapidly drive ciprofloxacin into the cornea where a drug reservoir is formed, which eventually releases slowly into aqueous humor, eliciting sustained therapeutic effect.