BACKGROUND: Stratum corneum lipids are arranged as intercellular membrane bilayers presumed to mediate the epidermal permeability barrier. Acute disruption in barrier function will initiate epidermal lipid synthesis, which can be prevented by occlusive membrane. Whereas, occlusion of the skin is known to cause an increased transepidermal water loss(TEWL) and enhanced percutaneous absorption of a variety of compounds. OBJECTIVE: Previous reports with electron microscopy showed varying sizes of lacunae and disorganized intercorneocyte lipids after tape stripping and occlusion with a water impermeable membrane on the murine skin. Hence we studied the effects on stratum corneum lipids and changes in barrier function after occlusion with a water-impermeable membrane. METHODS: Male hairless mice were occluded with one finger of a Latex glove for 24, 48 and 60 hours. After occlusion, TEWL was measured and biopsy specimens were taken from skin. For electron microscopic examination the samples were treated with osmium tetroxide, ruthenitum tetroxide, and tracer (lanthanum) and infrared spectroscopy were also applied. RESULTS: Occlusion with a water-impermeable membrane on the skin induced higher TEWL Values and greater penetration of the tracer than normal. Alterations of the lipid bilayer membrane and lacunae forwation in the stratum corneum interstices were also induced after 24 hours of occlusion. However, the orderness of the lipid alkyl chain in the stratum corneum was not changed until 60 hours of occlusion. CONCLUSION: These studies indicate that the increased epidermal permeability after occlusion may be due to the abnormal lipid membrane structures and volume expansion of existing lacunar domains in the stratum corneum interstices.
Animals ; Biopsy ; Fingers ; Humans ; Lanthanum ; Latex ; Lipid Bilayers ; Male ; Membranes ; Mice ; Mice, Hairless* ; Microscopy, Electron ; Osmium Tetroxide ; Permeability ; Skin ; Skin Absorption ; Spectrum Analysis ; Water

BACKGROUND: Glycolic acid has become popular and could provide an alternative choice to the current depigmenting agent. Vitamin C has been known as strong reducing agent and is supposed to retard synthesis of melanin pigment. Iontophoresis is emerging technologies capable of enhancing drug penetration through stratum corneum. Iontophoretic drug delivery may be easier following the chemical enhancer pretreatment OBJECTIVE: We evaluated the efficacy of vitamin C-iontophoresis and glycolic acid peeling for melasma. METHODS: 34 patients with facial melasma were treated with 30% glycolic acid peeling or vitamin C-iontophoresis or 30% glycolic acid peeling combined with vitamin C-iontophoresis. The treatment was performed weekly for a period of 12 weeks. Iontophoresis was performed for 6 minutes under a constant direct current of 0.3-1.0 mA/cm2. The exposure time for glycolic acid were 2 minutes. Before and after 12 weeks treatment, the state of melasma was documented using by the modified version of Melasma Area and Severity Index(mMASI) and Mexameter MX16(R). We also measured vitamin C2-phosphate flux by in vitro iontophoresor and HPLC assay. RESULTS: The mean scores of both mMASI and Mexameter MX16(R) after 12-week treatment were lower than those of baseline in all groups(p<0.05). Increasing vitamin C2-Phosphate concentration and increasing current density correlated with larger flux, and the flux in the first 40 minutes of the experiment appeared to be constantly larger than the steady-state flux during the period of the rest of the experiment, regardless of the current density. Pretreatment by peeling with glycolic acid did not significantly affect the vitamin C2-Phosphate flux through normal skin in vitro. CONCLUSION: Pretreatment by peeling with glycolic acid did not have a major impact on the vitamin C2-Phosphate flux in melasma patient.
Ascorbic Acid ; Chromatography, High Pressure Liquid ; Humans ; Iontophoresis ; Melanins ; Melanosis* ; Skin ; Vitamins*

The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4–fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis.
Acetaminophen ; Dendrimers* ; Dermis ; Electroosmosis* ; Epidermis ; Fluorescein-5-isothiocyanate ; Hair Follicle ; Iontophoresis ; Methanol ; Microscopy, Confocal ; Skin*