Improving Dermal Delivery of Rose Bengal by Deformable Lipid Nanovesicles for Topical Treatment of Melanoma.

Cutaneous melanoma is one of the most aggressive and metastatic forms of skin cancer. However, current therapeutic options present several limitations, and the annual death rate due to melanoma increases every year. Dermal delivery of nanomedicines can effectively eradicate primary melanoma lesions, avoid the metastatic process, and improve survival. Rose Bengal (RB) is a sono-photosensitizer drug with intrinsic cytotoxicity toward melanoma without external stimuli but the biopharmaceutical profile limits its clinical use. Here, we propose deformable lipid nanovesicles, also known as transfersomes (TF), for the targeted dermal delivery of RB to melanoma lesions to eradicate them in the absence of external stimuli. Considering RB's poor ability to cross the stratum corneum and its photosensitizer nature, transfersomal carriers were selected simultaneously to enhance RB penetration to the deepest skin layers and protect RB from undesired photodegradation. RB-loaded TF dispersion (RB-TF), prepared by a modified reverse-phase evaporation method, were nanosized with a ζ-potential value below -30 mV. The spectrophotometric and fluorimetric analysis revealed that RB efficiently interacted with the lipid phase. The morphological investigations (transmission electron microscopy and small-angle X-ray scattering) proved that RB intercalated within the phospholipid bilayer of TF originating unilamellar and deformable vesicles, in contrast to the rigid multilamellar unloaded ones. Such outcomes agree with the results of the in vitro permeation study, where the lack of a burst RB permeation peak for RB-TF, observed instead for the free drug, suggests that a significant amount of RB interacted with lipid nanovesicles. Also, RB-TF proved to protect RB from undesired photodegradation over 24 h of direct light exposure. The ex vivo epidermis permeation study proved that RB-TF significantly increased RB's amount permeating the epidermis compared to the free drug (78.31 vs 38.31%). Finally, the antiproliferative assays on melanoma cells suggested that RB-TF effectively reduced cell growth compared to free RB at the concentrations tested (25 and 50 µM). RB-TF could potentially increase selectivity toward cancer cells. Considering the outcomes of the characterization and cytotoxicity studies performed on RB-TF, we conclude that RB-TF represents a valid potential alternative tool to fight against primary melanoma lesions via dermal delivery in the absence of light.

Low-fluence laser-facilitated platelet-rich plasma permeation for treating MRSA-infected wound and photoaging of the skin.

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters.

Cutaneous permeation is a critical parameter when topical application of sunscreens containing antioxidants is considered. The aim of this study was to evaluate the cutaneous penetration of most marketed UV-filters combined with trans-resveratrol (RES) and beta-carotene (BTC) since few studies report skin penetration when such compounds are applied. Formulations containing octocrylene, octyl methoxycinnamate, avobenzone and bemotrizinole were prepared and supplemented or not with BTC, or with RES, or with both compounds in combination. Penetration studies were performed using Franz vertical diffusion cells and porcine ear skin as the biological membrane. The quantification of UV-filters and antioxidants in the stratum corneum (SC), viable epidermis plus dermis and receptor fluid was performed by HPLC. Results suggested that UV-filters and antioxidants did not permeate the skin but were retained for 12h post application. About 90% and 80%, respectively, of the total penetrated amount of UV-filters and antioxidants was found in the SC. Interestingly, it was observed that BTC, alone or combined with RES, reduced the skin retention of UV-filters on average by 63%. In conclusion, this study demonstrated that the combination of antioxidants and UV-filters in sunscreens is advantageous for cutaneous penetration, since BTC and BTC+RES improved sunscreen safety by reducing delivery of the four UV-filters in the study into SC and viable epidermis.

Photoprotective effects of apple peel nanoparticles.

Plants contain enriched bioactive molecules that can protect against skin diseases. Bioactive molecules become unstable and ineffective due to unfavorable conditions. In the present study, to improve the therapeutic efficacy of phytodrugs and enhance photoprotective capability, we used poly(D,L-lactide-co-glycolide) as a carrier of apple peel ethanolic extract (APETE) on permeation-enhanced nanoparticles (nano-APETE). The in vitro toxicity of nano-APETE-treated dermal fibroblast cells were studied in a bioimpedance system, and the results coincided with the viability assay. In addition, the continuous real-time evaluations of photodamage and photoprotective effect of nano-APETE on cells were studied. Among three different preparations of nano-APETE, the lowest concentration provided small, spherical, monodispersed, uniform particles which show high encapsulation, enhanced uptake, effective scavenging, and sustained intracellular delivery. Also, the nano-APETE is more flexible, allowing it to permeate through skin lipid membrane and release the drug in a sustained manner, thus confirming its ability as a sustained transdermal delivery. In summary, 50 µM nano-APETE shows strong synergistic photoprotective effects, thus demonstrating its higher activity on target sites for the treatment of skin damage, and would be of broad interest in the field of skin therapeutics.

Physicochemical modulation of skin barrier by microwave for transdermal drug delivery.

PURPOSE: To investigate mechanism of microwave enhancing drug permeation transdermally through its action on skin. METHODS: Hydrophilic pectin-sulphanilamide films, with or without oleic acid (OA), were subjected to drug release and skin permeation studies. The skins were untreated or microwave-treated, and characterized by infrared spectroscopy, Raman spectroscopy, thermal, electron microscopy and histology techniques. RESULTS: Skin treatment by microwave at 2450 MHz for 5 min promoted drug permeation from OA-free film without incurring skin damage. Skin treatment by microwave followed by film loaded with drug and OA resulted in permeation of all drug molecules that were released from film. Microwave exerted spacing of lipid architecture of stratum corneum into structureless domains which was unattainable by OA. It allowed OA to permeate stratum corneum and accumulate in dermis at a greater ease, and synergistically inducing lipid/keratin fluidization at hydrophobic C-H and hydrophilic O-H, N-H, C-O, C=O, C-N regimes of skin, and promoting drug permeation. CONCLUSION: The microwave technology is evidently feasible for use in promotion of drug permeation across the skin barrier. It represents a new approach in transdermal drug delivery.

Ex vivo decrease in uranium diffusion through intact and excoriated pig ear skin by a calixarene nanoemulsion.

Cutaneous contamination by radionuclides is a major concern in the nuclear industry. In case of skin exposure to uranium, no efficient emergency treatment is available to remove the actinide from the skin. For this purpose, we developed a nanoemulsion containing calixarene molecules displaying good chelating properties towards uranium. In this paper, we describe the ability of this formulation to trap uranium and limit its transfer from the cutaneous contaminated site into the blood. Uranium percutaneous diffusion kinetics was assessed with Franz cells over 24 h through intact and excoriated pig ear skin biopsies, after or without application of the nanoemulsion. Uranium distribution in the skin layers was analysed by SIMS microscopy. The results showed that prompt application of the calixarene nanoemulsion allows a 94% and 98% reduction of the amount of uranium diffused respectively through intact and excoriated skin. The formulation is still efficient in case of delayed application up to 30 minutes since the 24 h-uranium transfer through excoriated skin is reduced by 71%. Besides, no accumulation of uranium or uranium-calixarene chelate was observed in the different skin layers. In conclusion, this study demonstrated the efficiency of the calixarene nanoemulsion, which can be regarded as a promising treatment for uranium cutaneous contamination.

Fractional CO(2) laser-assisted drug delivery.

BACKGROUND AND OBJECTIVES: Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug. MATERIALS AND METHODS: Two Yorkshire swine were treated with single-hole CO(2) laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 microm. AFR was performed with a 10.6 microm wavelength prototype CO(2) laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. RESULTS: AFR created cone-shaped channels of approximately 300 microm diameter and 1,850 microm depth that were surrounded by a 70 microm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 microm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 microm from the holes (1,000, 1,800 microm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR. CONCLUSIONS: Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications.

Phototoxicity is not associated with photochemical tissue bonding of skin.

BACKGROUND AND OBJECTIVE: We have developed a light-activated method called photochemical tissue bonding (PTB) for closing wounds using green light and a photosensitizing dye (Rose Bengal-RB) to initiate photochemical crosslinking of wound surface proteins. These studies were designed to determine whether RB causes phototoxicity during closure of skin incisions with PTB. STUDY DESIGN/MATERIALS AND METHODS: RB phototoxicity was evaluated after sealing incisions in porcine skin ex vivo and rabbit skin in vivo using PTB (1 mM RB, 100 J/cm(2), 532 nm, 0.3 or 0.5 W/cm(2).) Dead cells were identified by pyknotic nuclei and eosinophilic cytoplasm on H&E-stained sections. The influence on RB phototoxicity of penetration of RB into the wound wall (by confocal microscopy), RB concentration in the tissue (by extraction), and fluence of 532 nm reaching depths in skin (calculated from skin optical properties) were investigated. RESULTS: No significant differences were found in the percent dead cells in PTB-treated and control incisions in porcine skin at 24 hours or in rabbit skin at 2 hours and 3 and 7 days after surgery. RB was retained in a approximately 100 microm wide band next to the wound wall. The mean RB concentration within this band was 0.42+/-0.03 mM. Monte Carlo modeling of light distribution indicated that the fluence rate decreased from the subsurface peak to 0.5 W/cm(2) in the mid-dermis (approximately 350 microm.) In vitro RB phototoxicity to dermal fibroblasts yielded an LD(50) of 0.50+/-0.09 J/cm(2) when the cells contained 0.46 mM RB. CONCLUSIONS: PTB does not cause phototoxicity when used to repair skin wounds even though the RB concentration and 532 nm fluence in the mid-dermis during PTB are much greater than the LD(50) for RB phototoxicity in vitro. These results indicate that phototoxicity is not a concern when using PTB for tissue repair.

Enhancement of skin optical clearing efficacy using photo-irradiation.

BACKGROUND AND OBJECTIVES: Tissue optical clearing technique based on immersion of tissues into optical clearing agents (OCAs) can reduce the scattering and enhance the penetration of light in tissue. However, the barrier function of epidermis limits the penetration of OCAs, and hence is responsible for the poor optical clearing efficacy of skin by topical action. In this study, a variety of light irradiation was applied to increase permeability of agents in skin and improve the optical clearing efficacy. STUDY DESIGN/MATERIALS AND METHODS: Different light sources with different dose, i.e, CO(2) laser, Nd:YAG laser (532 and 1,064 nm) with different pulse modes and Intense Pulsed Light (IPL) (400-700 and 560-950 nm) were used to irradiate rat skin in vivo, and then glycerol was applied onto the irradiated zone. VIS-NIR spectrometer was utilized to monitor the changes of reflectance. In vitro skin samples were also irradiated by Q-switched Nd:YAG laser (1,064 nm) and then treated by glycerol for 10-60 minutes. Based on the measurement of the reflectance and transmittance of the samples, the optical properties of skin and penetration depth of light were calculated. RESULTS: Results show that photo-irradiation with appropriate dose combining with the following glycerol treatment is able to reduce in vivo skin reflectance. Compared with the control group, the maximal changes in reflectance are ninefold at 575 nm and eightfold at 615 nm, respectively, which were caused by Q-switched 1,064-nm Nd:YAG laser irradiation and following glycerol treatment. The results for in vitro skin demonstrate that the joint action can significantly increase the optical penetration depth in samples. CONCLUSIONS: The combination of Q-switched Nd:YAG (1,064 nm) laser and glycerol could enhance optical skin clearing efficacy significantly. This study provides a non-invasive way to improve the optical clearing of skin, which will benefit the skin optical therapy.

Effects of ultraviolet radiation on the kinetics of in vitro percutaneous absorption of lavender oil.

The purpose of the present study is to investigate the influence of ultraviolet radiation on the rat skin absorption of lavender essential oil. The pure oil was extracted from Lavandula angustifolia by steam distillation. The chemical composition of lavender oil showed that terpenes are major compounds. In vitro, the essential oil was applied onto the rat skin. The amount of the compounds was determined using gas chromatography. Similarly, the amount of these compounds was analyzed for the skin exposed to ultraviolet radiation (UVAI) after 4, 8, 12 and 24 h. Our study demonstrated that the penetration profiles showed a cycle of charge-discharge (4 h/4 h, respectively). Our data point to the presence of reversible change in stratum corneum behavior. Interestingly, the ultraviolet radiation altered the cycle (charge-discharge) for terpenes (low lipophilicity) and increased the charge time. However, for terpenes (high lipophilicity), the ultraviolet radiation decreased the charge amplitude.

A combined approach of chemical enhancers and sonophoresis for the transdermal delivery of tizanidine hydrochloride.

The effects of chemical enhancers and sonophoresis on the transdermal permeation of tizanidine hydrochloride (TIZ) across mouse skin were investigated. Parameters including drug solubility, apparent partition coefficient (APC), drug permeation, and degradation in skin were determined. Low frequency ultrasound was also applied in the presence and absence of chemical enhancers to assess whether drug permeation improved. APC values indicated that TIZ preferentially partitions into intercellular spaces and does not form a reservoir, with the drug also exhibiting good enzymatic stability in skin. Most of the enhancers studied significantly increased the permeation rate of TIZ through full thickness mouse skin in comparison with TIZ formulated in phosphate buffer. Maximum enhancement was observed for TIZ formulated as a suspension in 50% v/v aqueous ethanol containing 5% v/v citral. Sonophoresis significantly (p < 0.05) increased the cumulative amount of TIZ permeating through the skin at 15 and 30 min in comparison to passive diffusion. A synergistic effect was noted when sonophoresis was applied in the presence of chemical enhancers. The results suggest that the formulation of TIZ with an appropriate penetration enhancer may be useful in the development of a therapeutic system to deliver TIZ across the skin for a prolonged period, i.e. 24 hr. The application of ultrasound in association with chemical enhancers, such as the combination of 5% v/v citral in 50% v/v aqueous ethanol, could further serve as a non-oral and non-invasive drug delivery modality for the immediate therapeutic effect of muscle relaxants such as TIZ.

Erbium:YAG laser enhances transdermal peptide delivery and skin vaccination.

Transdermal delivery of peptides and the related vaccines is attractive for treatment and prevention of diseases. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The objective of this study was to enhance and control skin permeation of peptides and related vaccines using an erbium:yttrium-aluminum-garnet (Er:YAG) laser. The amount of peptide transported through nude mouse skin was measured using a Franz diffusion apparatus. The SC layer was partly ablated by an Er:YAG laser, resulting in a greater enhancement effect on peptide delivery. A thinned and discontinuous SC layer was observed after laser exposure. The flux of peptides across skin treated with a laser at various fluences was 3-140-fold higher than that across intact skin. The molecular size, lipophilicity, and sequence of the peptides were found to play important roles in modulating the enhancement of activity. The result of confocal laser scanning microscopy (CLSM) indicated a significant increase in the skin deposition of peptides into laser-treated skin. In an in vivo study, mouse skin was treated with the laser followed by skin vaccination with a lysozyme antigen. It was demonstrated for the first time that laser treatment with no adjuvant or penetration enhancer significantly enhanced the production of antibodies in the serum by 3-fold. To reveal the mechanisms underlying these changes, a proteomic technique combined with mass spectrometry was used. This is, to our knowledge, the first report of a laser being used to immunize intact animals.

Transdermal penetration of UV filters.

A penetration study of 2-ethylhexyl-4-methoxycinnamate (EHMC), 4-methyl benzylidenecamphor (MBC), butyl methoxydibenzoylmethane (BMBM), 2-ethylhexyl-2,4,5-trimethoxycinnamate (EHTMC) and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate (TMB) through baby mouse skin (Mus musculus Linn.) was carried out using a vertical Franz diffusion cell. At 4.4 mg/cm(2) coverage of UV filter on the skin, 2.98 +/- 0.38, 1.15 +/- 0.14 and 0.80 +/- 0.28% of the applied EHMC, MBC and BMBM were detected in the receptor fluid at 24 h after application. Penetrations of UV filter in an ethanolic solution and lotion forms were comparable. EHTMC and TMB showed insignificant penetration across the baby mouse skins. Baby mouse skins kept at 4, -20 and -80 degrees C gave similar EHMC penetration results. Penetrations of EHMC, BMBM, EHTMC and TMB across human epidermis were carried out upon 5 volunteers using the suction blister technique. The results also confirmed the significant penetrations of EHMC and BMBM and the insignificant penetrations of EHTMC and TMB.

In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen.

Sunscreens, whose main function is to protect the skin against the harmful effects of solar irradiation, should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue. The goal of this work was to assess the penetration of titanium dioxide (TiO(2)) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT), included in a broad-spectrum sunscreen formulation, into human skin in vivo, using the tape stripping method, and in vitro, using a compartmental approach. An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application. TiO(2) and MBBT were quantified using colorimetric assay and HPLC analysis, respectively. The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO(2) in skin sections. More than 90% of both sunscreens was recovered in the first 15 tape strippings. In addition we have shown that the remaining 10% did not penetrate the viable tissue, but was localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT was detected in the receptor medium, and no TiO(2) was detected in the follicle, viable epidermis or dermis. Thus, this in vivo and in vitro penetration study showed an absence of TiO(2) penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT. However, differences in distribution within the stratum corneum reinforced the need for a complementary approach, using minimally invasive in vivo methodology and in vitro compartmental analysis. This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions.

Laser-assisted penetration of allergens for patch testing.

BACKGROUND: Patch-test patients often complain of itching and inconvenience. OBJECTIVE: To demonstrate (1) the usefulness of laser-assisted alteration of the stratum corneum to enhance allergen delivery and (2) patient satisfaction with this procedure. METHODS: The LAD-01 (erbium:yttrium-aluminum-garnet) laser unit was used to alter stratum corneum from patients with known sensitivity to nickel or Kathon CG. These allergens were then applied to the laser-pretreated sites for 60 minutes. Results were observed at 24, 48, and 96 hours and at 1 week. One patient who refused conventional patch testing was tested with an entire modified North American standard series tray with the laser patch-test technique. An additional patient with previously demonstrated positive atopy patch-test reactions to environmental organisms was retested with laser pretreatment to the same antigens. RESULTS: Three of three patients known to be sensitive to Kathon CG and eight of eleven known nickel-sensitive patients had positive reactions at the laser-pretreated sites. The patient who was tested with the entire standard series demonstrated relevant positive reactions to formaldehyde and to a textile resin. One subject with known reactions to three environmental organisms reproduced patch-test responses with laser pretreatment. No irritant reactions were noted. Patients reported no pain. CONCLUSION: With further modification, laser pretreatment may improve patient convenience and decrease irritant test reactions owing to occlusion.

Comparison of biophysical properties of skin measured by using non-invasive techniques in the KM mice following 595 nm pulsed dye, 1064 nm Q-Switched Nd:YAG and 1320 nm Nd:YAG laser non-ablative rejuvenation.

BACKGROUNDS/AIMS: The aim of the study was to compare the changes of the biophysical properties and to objectify the effects of 595 nm pulsed dye, 1064 nm Q-switched Nd:YAG and 1320 nm Nd:YAG lasers non-ablative rejuvenation by non-invasive techniques. METHODS: KM mice were used for the study. The 595 nm pulsed dye, 1064 nm Q-switched Nd:YAG and 1320 nm Nd:YAG laser treatments were evaluated with biophysical parameter measurements including skin elasticity, skin color, skin trans-epidermal water loss (TEWL) and skin hydration. RESULTS: All three lasers improved the biophysical properties in the skin of KM mice. In skin elasticity measurements, the 1064 nm laser treatment showed the lowest ratio (0.61+/-0.09) while the 1320 nm laser showed the highest one (0.76+/-0.07) on day 60. For erythema values, a significant increase was observed immediately after the 1064 nm laser treatment (196.67+/-19.17), but the lowest values occurred with the 1320 nm laser treatment (189.83+/-16.54). None of the three lasers resulted in obvious changes of skin melanin. TEWL increased immediately after laser irradiation, then began to recover and decreased 60 days after the 595 and 1064 nm laser treatments. With the 1320 nm laser treatment the TEWL began to decrease from day 7 and obtained the lowest mean values (5.23+/-1.13). The water-holding capacity increased initially for the 595 and 1320 nm laser irradiation, while decreased for the 1064 nm laser. At day 60 of the experiment, skin hydration values in all animals were superior to those of the controls. The 1320 nm laser treatment caused the highest ratio (1.29+/-0.26). Both the values of TEWL and skin hydration for the 1320 nm laser treated areas differed significantly from the other two lasers. CONCLUSIONS: Our data showed the 1064 nm Q-switched Nd:YAG laser treatment was most effective in improving the skins' mechanical properties, while the 1320 nm Nd:YAG laser can enhance greatly the skin barrier function and the water-holding capacity. Moreover, we demonstrated the biophysical properties differed considerably between different areas.

Natural radioactivity in sand used in thermal therapy at the Red Sea Coast.

The development of climatotherapy in Safaga opens the field of medical tourism in Egypt, in order to detect any harmful radiation that would affect the patients during treatment and is becoming important economic resource. Studies and survey of natural radiation and radioactivity in upper Egypt conducted since 1990, included monitoring of the concentration of natural radionuclides in environmental samples. The results of the study reveals that, for all sand samples, the mean activity concentration of 40K (618+/-122-548+/-82 Bq kg(-1)) are much higher than that of both 226Ra (25.3+/-14-20.6+/-10 Bq kg(-1)) and 232Th (21.4+/-10-22.4+/-10 Bq kg(-1)). Different radiation hazard indices were calculated, the radiation dose to which workers are subjected is not negligible (26.5-50.9 nGy h(-1)), although depending on the inhalation of dust.

Suppressed permeation of linoleic acid in a liposomal formulation through reconstructed skin tissue.

Since the liposomal formulation of linoleic acid (LA) exhibited an enhanced skin-whitening effect, the influence of liposomalization on the cutaneous absorption of LA was examined using a three-dimensional (3D) reconstructed skin model. Liposome entrapped [(14)C]-LA was applied on the skin model, and the permeation of LA through the skin was monitored. The permeation rate of LA in the liposomal formulation was found to be lower than that in the conventional formulation without liposomes, suggesting the increased retention time of LA in the skin by the liposomal formulation. Next, to investigate the dependence of the LA permeation on melanocyte conditions and intactness of the reconstructed skin model, the effect of UV irradiation on LA permeation was examined. Low-dose UVB irradiation (0.03 J/cm(2) for 3 times), which activated melanocytes in the skin, did not influence the extent of LA permeation, while high-dose irradiation (0.30 J/cm(2) for 3 times) enhanced the permeation of LA in both the conventional and liposomal formulation. The present results suggest the importance of skin intactness for LA permeation and that the 3D reconstructed skin model would be useful for evaluating the characteristics of skin-oriented cosmetics and drugs.