Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis.
Poor absorption and stability of peptides are the major obstacles concerning the development of therapeutically relevant iontophoretic devices for the transdermal delivery of peptides. The present study examined the impact of constant and pulsed (direct/alternating) current profiles on the transport and stability of two decapeptides LHRH and Nafarelin. The stability of these peptides was studied in a physiological buffer solution, with electrical current, and when the peptide solution was exposed to the stratum corneum or to the epidermal/dermal side of human skin. Pulsed direct current profile was shown to be the most efficient in transporting both LHRH and Nafarelin across the human epidermis. Furthermore, the percentage of intact LHRH in the receiver phase was slightly higher when a pulsed current profile was used. Both the peptides were stable in a physiological buffer and under the influence of current, but LHRH was degraded especially in contact with the dermal side of the skin. Altogether five hydrolytic degradation products of LHRH were observed, and they were identified by LC-ESI/MS and LC-ESI/MS/MS. No degradation products of Nafarelin were observed. It is concluded that the pulsed direct current profile may provide at least a partial solution for the transdermal delivery of peptides in terms of improved transport efficacy and peptide stability.
Raiman
Johanna
J
Divisions of Pharmaceutical Technology and Viikki Drug Discovery Technology Center, Department of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 University of Helsinki, Helsinki, Finland. johanna.raiman@helsinki.fi
Koljonen
Maija
M
Huikko
Katri
K
Kostiainen
Risto
R
Hirvonen
Jouni
J
D000279:Administration, Cutaneous; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004355:Drug Stability; D004817:Epidermis / Q000378:metabolism; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D013058:Mass Spectrometry; D017274:Nafarelin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D013997:Time Factors
D005300:Fertility Agents, Female; D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone