Effect of penetration enhancers on the permeation of the thyrotropin releasing hormone analogue pGlu-3-methyl-His-Pro amide through human epidermis.

The effect of the enhancers, cineole and ethanol, on the transdermal penetration of the tripeptide, pGlu-3-methyl-His2-Pro amide (M-TRH), across human epidermal membrane was studied by flow-through diffusion chambers. The aim of the study was to assess whether the biologically active analogue M-TRH displays similar transdermal penetration properties as those demonstrated earlier for the parental peptide, thyrotropin-releasing hormone (TRH) (Magnusson et al., 1997a Int. J. Pharm. 157, 113-121). Steady-state fluxes with a donor solution of phosphate-buffered saline (PBS) were 0.34 +/- 0.01 microgram/cm2h for M-TRH and 0.27 +/- 0.01 microgram/cm2h for TRH. Measured over 30 h the total amount penetrated was 8.6 +/- 1.0 and 7.8 +/- 1.7 micrograms/cm2, respectively. In the presence of 50% ethanol, the flux of the peptides increased approximately 3-fold. A donor solution of 3% cineole, in combination with 47% ethanol, increased the penetration of M-TRH to 1.60 +/- 0.02 micrograms/cm2h, compared to 0.92 +/- 0.03 microgram/cm2h for TRH, as reported previously. The corresponding total amount penetrated over 30 h was 41.5 +/- 4.9 and 24.9 +/- 1.7 micrograms/cm2, respectively. Our data suggests that enhancers added together with the penetrant can theoretically induce changes in the permeability of the stratum corneum sufficient to promote the transdermal absorption of therapeutically relevant amounts of these peptides. This demonstrates the possibility to deliver classes of compounds that have been viewed as not suitable for transdermal administration.

Terpene-enhanced transdermal permeation of water and ethanol in human epidermis.

The study was performed to investigate the effect of penetration enhancers on the stratum corneum barrier. Epidermal membranes were prepared from freeze-stored (-70 degrees C) Caucasian breast skin and mounted in a flow-through diffusion cell. The validity of the freeze storage procedure was verified by measurement of [3H]-water penetration. The effect of the cyclic terpene, carveol, on the transdermal penetration of water and ethanol was studied in vitro. Control ethanol and water penetration measured with a donor solution of 50% ethanol/PBS (w/w) was 1.9+/-0.2 and 3.6+/-0.5 x 10(-3) cm/h. The addition of 3% carveol to the donor solution increased the permeation of ethanol and water after 4 h to 8.3+/-1.1 and 12.5+/-1.9 x 10(-3) cm/h, respectively. In a separate experiment, terpinen-4-ol and alpha-terpineol were also tested, in addition to carveol, for effect on tritium flux. No significant difference in maximum tritium flux was obtained between the three terpenes studied. The maximum increase in permeability coefficients of carveol, terpinen-4-ol and alpha-terpineol was 10.6, 8.7 and 10.9, respectively.

Surgical treatment of skin lesions induced by sulfur mustard ("mustard gas")--an experimental study in the guinea pig.

Sulfur mustard has been known as a chemical warfare agent since 1915 and its biological effects, e.g. acting as an alkylating agent reacting with nucleophiles in proteins and nucleic acids, are well known. Still, there is today no specific antidote against or treatment of sulfur mustard induced cutaneous lesions. Recently, a technique of treating thermal burns with early surgical excision followed by skin grafting has been established. The present study was undertaken to evaluate, if a similar technique could be of value in the treatment of sulfur mustard lesions. Under anaesthesia, guinea pigs were exposed to sulfur mustard vapour, followed six hours later by excision of the exposed skin segment. In animals where the skin defect was primary sutured, healing time was significantly shorter and increase in body mass greater compared to conservatively treated controls. No such differences were found if excision was followed by full thickness skin grafting. Further studies in other species are suggested to clarify the possible role of surgical excision of sulfur mustard skin lesions, followed by skin transplantation, in humans.