Enhanced transdermal delivery of 5‐aminolevulinic acid and a dipeptide by iontophoresis

Abstract

Poor skin permeability limits the application of peptides to the skin. Enhanced skin permeation could facilitate the development of new therapies for dermatologic and cosmeceutical applications. The aim of this study was to investigate the application of iontophoresis to the delivery of small peptide model compounds (5-aminolevulinic acid and L-alanine-L-tryptophan) across human skin. Under the conditions tested, iontophoresis increased the in vitro permeability coefficient of ALA.HCl across human epidermis from 7 X 10(-5) cm/h with passive diffusion to 110 x 10(-5) cm/h with iontophoresis. D-Glucose permeation elucidated the iontophoretic electrotransport of ALA.HCl to have contributions of both electrorepulsion and electroosmosis. The L-alanine-L-tryptophan permeability coefficient was increased from 1.5 x 10(-5) cm/h to 35 x 10(-5) cm/h with iontophoretic application. Iontophoretic delivery of the dipeptide increased markedly at lower pH because of an increase in electrorepulsive transport. The study demonstrates that iontophoresis can enhance epidermal permeation of a small peptide and peptide-like drug by up to 15- and 22-fold under the conditions tested.

Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac

“…Sampling was approved by the Human Research Ethics Committee of Curtin University and was conducted in compliance with the guidelines of the National Health and Medical Research Council of Australia. Epidermal sheets were obtained and stored as previously described [38]. …”

Delivery of drugs applied topically to the skin

“…Insulin, ketoprofen and vaccines [93,95,165] Increased driving force technologies Iontophoresis Transdermal delivery by a small direct current Charged molecules, peptides, proteins and indomethacin [97,98,166] Dermaportation or magnetophoresis Delivery using static or variable magnetic fields Benzoic acid, terbutaline sulfate, 5-ALA, Ala-Trp (dipeptide) and naltrexone [100][101][102][103][104] ALA: Aminolevulinic acid.…”

“…They suggested that the magnetic fields increased the driving force on the molecules and caused a temporary alteration in skin structure. More recently, work from Australia has found an enhanced penetration of 5-aminolevulinic acid [101], a dipeptide, Ala-Trp [102], and naltrexone [103] through excised human epidermis with application of pulsatile magnetic fields. In addition, the magnetic fields caused enhanced penetration of 10-nm gold nanoparticles into the viable epidermis of excised human full-thickness skin [103].…”

“…More recently, work from Australia has found an enhanced penetration of 5-aminolevulinic acid [101], a dipeptide, Ala-Trp [102], and naltrexone [103] through excised human epidermis with application of pulsatile magnetic fields. In addition, the magnetic fields caused enhanced penetration of 10-nm gold nanoparticles into the viable epidermis of excised human full-thickness skin [103]. Work from this group is continuing with static magnetic fields generated by thin films that could be easily incorporated into a multifunctional transdermal patch.…”

Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy

“…As mentioned earlier, iontophoresis can be an effective method for increasing the penetration of ALA through the skin. Krishnan et al [22] first looked at using iontophoresis to deliver small peptide compounds (ALA and L-alanine-L-tryptophan) across human skin. Compared to passive diffusion, iontophoresis increased the rate of transport of L-alanine-L-tryptophan and ALA by 15- and 22-fold, respectively.…”