Enhanced transdermal delivery of a dipeptide by dermaportation

Abstract

Poor skin permeability and stability limits the application of peptides to the skin. Enhanced skin permeation could offer new therapies for a range of dermatological and cosmetic applications. The aim of this study was to investigate the application of a novel magnetic field enhancement technology to peptide delivery across the skin. Ala-Trp was used as a model dipeptide. Stability of the dipeptide in a range of conditions and with exposure to skin was determined. Dermaportation-magnetic field technology increased the in vitro permeability coefficient of Ala-Trp across human epidermis from 7.7 x 10(-4) cm/h with passive diffusion to 1.94 x 10(-2) cm/h with Dermaportation. Ala-Trp was unstable with exposure to human epidermis. Following permeation across the epidermis, a degradation product was detected in the receptor solution with the amount increasing up to 6 h. Given the susceptibility of peptides to degradation in the skin it is essential that they are delivered rapidly across the skin in order to maximize the opportunity for delivery of the native peptide. Dermaportation offers a potential new delivery method for skin delivery of peptides for a range of dermatological and cosmetic applications.

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].…”

Electrical and Physical Methods of Skin Penetration Enhancement

“…121,122 Research into dermaportation and other magnetic enhancement techniques is being carried out at Curtin University, Western Australia. Dermaportation has been reported to enhance penetration of 5 -aminolevulinic acid 123 and a dipeptide, Ala -Trp, 124 through human epidermis in vitro . Like Murthy et al, 121,122 Namjoshi et al 124 suggest that the mechanism of enhancement involves both a direct magnetic repulsion on the penetrants and increased permeability due to a rearrangement of the SC lipid bilayers.…”

“…Dermaportation has been reported to enhance penetration of 5 -aminolevulinic acid 123 and a dipeptide, Ala -Trp, 124 through human epidermis in vitro . Like Murthy et al, 121,122 Namjoshi et al 124 suggest that the mechanism of enhancement involves both a direct magnetic repulsion on the penetrants and increased permeability due to a rearrangement of the SC lipid bilayers. Recent work by Krishnan et al 125 showing that dermaportation caused enhanced naltrexone penetration though human epidermal membranes, but not through silicone membranes, provides some evidence to support a direct effect of pulsed magnetic fi elds on skin.…”

Study of magnetic silk fibroin nanoparticles for massage-like transdermal drug delivery

“…It is believed that the interaction between a pulsed electromagnetic field and the skin could enhance transdermal drug delivery, 20,21 and an electromagnetic field has been shown to induce a change in structures of keratinocytes. 22 Recent developments have also confirmed that the hair follicles play a significant role in transdermal permeation and that the application of massage has a positive effect in follicular penetration.…”