Lower Layers Of Skin Research Articles

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery.

(1) Background: Chitosan-gelatin-based thermosensitive hydrogel containing 5FU-alginate nanoparticles was formulated for the effective and sustained delivery of 5FU to the skin. (2) Methods: Alginate, a polysaccharide was used for the formulation of nanoparticles using a spray drying technique. Size, zeta potential, and surface morphology were investigated using a zetasizer and scanning electron microscope. The hydrogel was fabricated using chitosan and gelatin. Several important analyses were used to characterize these prepared topical hydrogels. The pH, visual transparency, rheological behavior, and swelling index of the prepared hydrogels were evaluated. The in vitro release studies were performed at different pH (5.5 and 7.4) and temperature (32 and 37 °C) conditions using a Franz diffusion cell. Ex vivo permeation and in vivo studies were performed using Sprague Dawley rats. (3) Results: Results show that spherical nanoparticles were produced at sizes of 202–254 nm and with zeta potentials of −43 to −38 mV. The prepared nanoparticles were successfully incorporated into chitosan-gelatin-based hydrogels using a glycerol 2-phosphate disodium salt hydrates crosslinker. Drug polymers and excipients compatibility and formulation of hydrogels was confirmed by ATR-FTIR results. The pH of the prepared hydrogels was in accordance with the skin pH. The viscosity of prepared hydrogel increased with temperature increase and phase transition (sol-gel transition) occurred at 34 °C. The release of drug was sustained in case of nanoparticles incorporated hydrogels (5FU-Alg-Np-HG) as compared to nanoparticles (5FU-Alg-Np) and simple hydrogels (5FU-HG) (ANOVA; p < 0.05). The premature and initial burst release of 5FU was prevented using 5FU-Alg-Np-HG. The release mechanism of 5FU from the 5FU-Alg-Np-HG diffusion was followed by swelling and erosion, as suggested by Korsmeyer-Peppas model. The prepared hydrogel proved to be non-irritant. Ex vivo permeation study across rat’s skin suggests that permeability of nanoparticles (5FU-Alg-Np) was higher than the 5FU-Alg-Np-HG (ANOVA; p < 0.05). However, skin-related drug retention of 5FU-Alg-Np-HG was significantly higher than the 5FU solution, 5FU-Alg-Np, and 5FU-HG (ANOVA; p < 0.05). This was due to swelling of hydrogels in the lower layers of skin where the temperature is 37 °C. The higher concentration of 5FU in the skin is helpful for treatment of local skin cancer, such as melanoma, and actinic keratosis. In vivo results also confirmed maximum AUC, t1/2, and skin-related drug retention of 5FU-Alg-Np-HG. (4) Conclusions: Chitosan-gelatin-based hydrogels containing 5FU-Alg-Np possess exceptional properties, and can be used for the sustained delivery of 5FU for the treatment of local skin cancers.

A Review on Role of Essential Oil as Penetration Enhancer in Transdermal Drug Delivery System

The use of essential oils and their constituents as skin penetration enhancers for transdermal drug delivery, as well as the mode of action and potential toxicity. Essential oils and their toxic components have the ability to penetrate the skin and improve the penetration of various drugs from topical formulations into the lower skin layers by various modes of action. (1) disintegration of the highly organised intercellular lipid structure between corneocytes in the Stratum Corneum, (2) association with the intercellular domain of proteins, causing conformational change, and (3) Increase a drug's partitioning essential oils and their components are easily metabolised, do not persist in the body, and are quickly excreted after application to the skin, indicating that they can be used as healthy penetration enhancers. Essential oils and their constituents can be preferable to synthetics as healthy and effective permeation enhancers for promoting the percutaneous absorption of hydrophilic and lipophilic drugs from topical formulations into the lower skin layers. they have been used successfully as secure penetration enhancers. To address these issues, the Transdermal Drug Delivery System (TDDS) was developed, which would increase the clinical effectiveness and safety of medications by allowing for more accurate (i.e., location specific) positioning inside the body, minimising both the size and number of doses. Many medications are now taken orally, but they are not as successful as they can be. This article offers a description of the transdermal drug delivery mechanism and forms of transdermal patches, as well as the use of polymer as a Transdermal Drug Delivery System, preparation processes, and physicochemical assessment methods and the various forms of transdermal systems currently on the market, with an emphasis on recent developments in Transdermal Drug Delivery Systems, which may serve as a forum for prescription drug dosage form research and development for Transdermal Drug Delivery.

Evaluation of the Transepidermal Penetration of a Carnosine Complex in Gel Formulation by 3D Skin Models

Carnosine has several physiological roles, from intracellular pH buffering to antioxidant activities, which all depend on bioavailability. This study was conducted in a human skin 3D model and focuses on the effects of the topical delivery of carnosine, from a dermo-cosmetic gel, through the stratum corneum in the presence of a magnesium ion as a complexing agent. To evaluate possible enhancement for small peptide delivery to the skin from simple cosmetic formulations, we discovered that complexation was able to improve the delivery of carnosine into human skin 3D models by application in gel formulation. The concentrations of carnosine released in the underlying media and those that remained in the reconstructed human epidermis (RHE) tissues after 24 and 48 h exposure were measured. Moreover, the influence of magnesium ions was also evaluated comparing the same formulation with and without the salt. The results obtained in this study support hypothesis that magnesium can influence the delivery of small peptides and that the gel formulation based on the carnosine-magnesium complex allows for superior delivery of carnosine in the lower skin layer at a concentration up to 60% more than carnosine alone.

Myosin phosphatase accelerates cutaneous wound healing by regulating migration and differentiation of epidermal keratinocytes via Akt signaling pathway in human and murine skin

Wound healing is a complex sequence of cellular and molecular processes such as inflammation, cell migration, proliferation and differentiation. ROCK is a widely investigated Ser/Thr kinase with important roles in rearranging the actomyosin cytoskeleton. ROCK inhibitors have already been approved to improve corneal endothelial wound healing. The purpose of this study was to investigate the functions of myosin phosphatase (MP or PPP1CB), a type-1 phospho-Ser/Thr-specific protein phosphatase (PP1), one of the counter enzymes of ROCK, in skin homeostasis and wound healing. To confirm our hypotheses, we applied tautomycin (TM), a selective PP1 inhibitor, on murine skin that caused the arrest of wound closure. TM suppressed scratch closure of HaCaT human keratinocytes without having influence on the survival of the cells. Silencing of, the regulatory subunit of MP (MYPT1 or PPP1R12A), had a negative impact on the migration of keratinocytes and it influenced the cell-cell adhesion properties by decreasing the impedance of HaCaT cells. We assume that MP differentially activates migration and differentiation of keratinocytes and plays a key role in the downregulation of transglutaminase-1 in lower layers of skin where no differentiation is required. MAPK Proteome Profiler analysis on human ex vivo biopsies with MYPT1-silencing indicated that MP contributes to the mediation of wound healing by regulating the Akt signaling pathway. Our findings suggest that MP plays a role in the maintenance of normal homeostasis of skin and the process of wound healing.

Microwave-aided skin drug penetration and retention of 5-fluorouracil-loaded ethosomes

ABSTRACTObjectives: Skin drug retention is required in local treatment of skin cancer. This study investigated the interplay effects of ethosomes and microwave in transdermal drug delivery. Skin pre-treatment by microwave and applied with liquified medicine is deemed to ‘cement’ the skin thereby raising skin drug deposition.Methods: 5-fluorouracil-loaded ethosomes were prepared and subjected to size, zeta potential, morphology, drug content, drug release and skin permeation tests. The molecular characteristics of untreated, microwave and/or ethosome-treated skins were examined by Fourier transform infrared and raman spectroscopy, thermal and electron microscopy techniques.Results: The skin drug retention was promoted using larger ethosomes with negative zeta potentials that repelled anionic lipids of skin and hindered vesicle permeation into deep layers. These ethosomes had low ethanol content. They were less able to fluidize the lipid and defluidize the protein domains at epidermis to enlarge aqueous pores for drug permeation. Pre-treatment of skin by 2450 MHz microwave for 2.5 min further increased skin drug penetration and retention of low ethanol ethosomes and provided lower drug permeation than cases treated for 1.15 min and 5 min. A 2.5 min treatment might be accompanied by specific dermal protein fluidization via C=O moiety which translated to macromolecular swelling, narrowing of intercellular spaces at lower skin layers, increased drug retention and reduced drug permeation.Conclusion: Ethosomes and microwave synergized to promote skin drug retention.

Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review.

In this paper, we focused on essential oils and their constituents as skin penetration enhancers for transdermal drug delivery, mechanism of their action as well as their possible toxicity. Essential oils and their volatile constituents can penetrate through the skin as well as enhance penetration of different drug from topical formulation into the lower skin layers using different mechanisms of action based on (1) disintegration of the highly ordered intercellular lipid structure between corneocytes in stratum corneum, (2) interaction with intercellular domain of protein, which induces their conformational modification, (3) increase the partitioning of a drug. After application to the skin, essential oils and their components are rapidly metabolized, not accumulated in the organism and fast excreted what strongly suggest that they can be successfully use as safe penetration enhancers. Essential oils and their constituents may be preferred over the traditionally used synthetics materials as safe and suitable permeation enhancers to promote the percutaneous absorption of hydrophilic and lipophilic drugs from topical formulation into the lower skin layers.

Dynamic model of thermal reaction of biological tissues to laser-induced fluorescence and photodynamic therapy

The aim of this work was to evaluate the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed ultraviolet (UV) laser (λ=337 nm) and a continuous-wave (cw) visible laser beam (λ=632.8 nm) using Monte Carlo modeling. Finite-element methodology was used for heat transfer simulation. The analysis of the results showed that heat is not localized on the surface, but is collected inside the tissue in lower skin layers. The simulation was made with the pulsed UV laser beam (used as excitation source in laser-induced fluorescence) and the cw visible laser (used in photodynamic therapy treatments), in order to study the possible thermal effects.

Improved Method for Determining Partition and Diffusion Coefficients in Human Dermis

Accurate values of partition and diffusion coefficients within the lower skin layers are among the information required to estimate skin concentrations of permeants following topical application. For highly lipophilic compounds these parameters also play a significant role in determining systemic absorption rates. In this study methodology is described for making more accurate in vitro measurements of partition and diffusion coefficients in dermis. Isolated human dermis obtained from surgical reduction was mounted in side-by-side diffusion cells in the presence and absence of a dialysis membrane (5000 MW cut-off) placed between the dermis and the donor solution. Permeation of N,N-diethyltoluamide (DEET) and diclofenac across the composite membrane system, as well as steady-state skin concentrations, were measured by radiochemical techniques. For the highly protein bound compound, diclofenac, dermis permeability, and partition coefficient determined in the presence of the dialysis membrane were significantly higher than those determined in its absence. No significant differences were observed for the moderately protein bound DEET. The results show that, in the absence of a stratum corneum barrier, attention must be given to the diffusion of soluble proteins in order to obtain accurate estimates of transport and partitioning parameters for highly protein bound solutes in dermis.

Enhanced chlorhexidine skin penetration with eucalyptus oil

BackgroundChlorhexidine digluconate (CHG) is a widely used skin antiseptic, however it poorly penetrates the skin, limiting its efficacy against microorganisms residing beneath the surface layers of skin. The aim of the current study was to improve the delivery of chlorhexidine digluconate (CHG) when used as a skin antiseptic.MethodChlorhexidine was applied to the surface of donor skin and its penetration and retention under different conditions was evaluated. Skin penetration studies were performed on full-thickness donor human skin using a Franz diffusion cell system. Skin was exposed to 2% (w/v) CHG in various concentrations of eucalyptus oil (EO) and 70% (v/v) isopropyl alcohol (IPA). The concentration of CHG (μg/mg of skin) was determined to a skin depth of 1500 μm by high performance liquid chromatography (HPLC).ResultsThe 2% (w/v) CHG penetration into the lower layers of skin was significantly enhanced in the presence of EO. Ten percent (v/v) EO in combination with 2% (w/v) CHG in 70% (v/v) IPA significantly increased the amount of CHG which penetrated into the skin within 2 min.ConclusionThe delivery of CHG into the epidermis and dermis can be enhanced by combination with EO, which in turn may improve biocide contact with additional microorganisms present in the skin, thereby enhancing antisepsis.

Glucose Partition Coefficient and Diffusivity in the Lower Skin Layers

This work aims to estimate the diffusivity and partitioning of glucose in the dermis and the viable epidermis of human skin. The partition coefficient of glucose between phosphate-buffered saline and dermis, tape-stripped epidermis (TSE), stratum corneum (SC), and split-thickness skin, was measured in vitro using human cadaver skin. Glucose permeability across dermis and tape-stripped split-thickness skin (TSS) was measured using side-by-side diffusion cells. Glucose desorption from TSE and human epidermal membrane (HEM) was measured. All measurements were conducted at 32 degrees C. The partition coefficient for glucose [mean +/- SD (no. of samples)] was 0.65 +/- 0.09 (n = 25) for dermis, 0.81 +/- 0.06 (n = 10) for TSE, and 0.53 +/- 0.12 (n = 9) for SC. Glucose diffusivity in dermis was calculated to be 2.64 +/- 0.42 x 10(-6) cm2/s (n = 14). Glucose diffusivities in the viable epidermis estimated from TSS permeation, TSE desorption, and HEM desorption were 0.075 +/- 0.050 x 10(-6) cm2/s (n = 5), 0.037 +/- 0.018 x 10(-6) cm2/s (n = 4), and 1.0 +/- 0.6 x 10(-6) cm2/s (n = 4), respectively. The tissue/buffer partition coefficient of glucose in all skin layers was found to be less than unity, suggestive of excluded volumes in each layer. Glucose diffusivity in human dermis was found to be one third of its value in water, indicative of hindered diffusion related to the structural components of the tissue. A substantially lower value for glucose diffusivity in viable epidermis is suggested.

AFM, EDS and XRD Microstructural Characterizations of Pd-Ag/PSS Membranes

In the present investigation, dense, defect free palladium and palladium-silver alloy membranes were prepared on porous stainless steel by means of the sequential electroless plating technique. Full characterizations of the Pd-Ag/PSS membranes were performed using scanning electron microscopy (SEM), energy dispersive spectroscopic analysis (EDS), atomic force microscopy (AFM), and an X-ray diffractometer (XRD). AFM images showed that in the electroless plating process, lower skin layer roughness and a lower deposition rate were related. Although deposition was conducted through a sequential process, the surfaces on or inside the substrate showed homogenous deposition, as determined through EDS analysis. XRD reflection peaks indicated that the palladium and silver together formed a homogeneous alloy after annealing. The relationship between the average lattice spacing and peak positions can be used to estimate the membrane composition.

Fluocinolone acetonide topical oil for scalp psoriasis

Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.

Genetics of color of the ornamental carp: inheritance of underlying dark coloration

In ornamental carps from the collection of the Experimental Station, All-Russia Research Institute of Fresh-Water Fisheries, fish with a dirty dark tint of body color among orange and white fish were found. This coloration was shown to be due to the presence of black pigment cells in the lower skin layer. In the outer skin layers these cells were almost entirely absent. This color type was found to be determined by the presence of at least one of alleles B1' or B2' of digenic system B1, B2, which is responsible for the development of melanophores in fish skin. Each of the genes of this digenic system is represented by three alleles with the following order of dominance: B > B' > b.

In Vivo Exposure to Ozone Depletes Vitamins C and E and Induces Lipid Peroxidation in Epidermal Layers of Murine Skin

To evaluate skin susceptibility to ozone (O 3) and to localize possible oxidative damage within the skin layers, hairless mice were exposed to 10 ppm O 3 or air (0 ppm O 3) for 2 h. The mice were euthanized, the skin removed and frozen. Three skin layers (upper epidermis, lower epidermis/papillary dermis, and dermis) were separated, antioxidant concentrations ( α-tocopherol and ascorbic acid) and the lipid peroxidation product malondialdehyde (MDA) measured. In the upper epidermis, O 3 significantly depleted α-tocopherol (22%; p < .05) and ascorbic acid (55%; p < .01). These antioxidants were unchanged by O 3 in the lower skin layers. More remarkably, MDA increased ten-fold in the upper epidermis ( p < .001) and two-fold in the lower epidermis/papillary epidermis ( p < .05); it was unchanged in the dermis. Thus, exposure to O 3 in vivo depletes ascorbic acid and α-tocopherol and strongly induces lipid peroxidation in skin. High MDA concentrations measured in the upper epidermis suggest that O 3 reacts directly with fatty acids on the skin surface layers. These results further suggest that chronic exposure to lower O 3 concentrations found in urban smog could potentially have implications for skin health.

箱型射出成形品における成形過程を考慮した変形解析

Injection moulding is an established production technology for the forming of thermo-plastics resins. Recently, it has been applied to fibre reinforced thermoplastics (FRTP), and developments in this field are continuing. However, this method has still many problems, such as brittle weakness along weld-line, warping, incomplete filling and so on, especially for the fibre reinforced plastics dealt with here.In this paper, a simulation was carried out for a box product with thin wall by considering the velocity distribution resulting from the velocity difference in flow between the upper and lower skin layers. A box was unfolded onto one plane to convert a three-dimensional structure to a two-dimensional model. After the flow analysis, the fibre orientation analysis was carried out by assuming that fibres rotate according to the velocity gradient tensor obtained for each element by the flow analysis. Finally, an attempt was made to established the deformation analysis for determining the out-of-plane deflections based on the results of the fibre orientation analysis.In the experiments, the shape of flow front, fibre orientation and out-of-plane deflection were determined by the observation of short shot mouldings, soft X-ray photographs and moire-image interrence fringes, respectively. The numerical results were compared with the experimental observation. They showed a good agreement.

射出成形における箱形成形品の強化繊維配向の解析

The purpose of the investigation is to devise a procedure for the computer aided design of the injection moulding process for FRTP (Fibre Reinforced Thermo-Plastics), taking the fibre orientation into consideration.This system consists of a series of analyses of flow, the flow fibre orientation and warp. The state of the composites in the core layer is two-dimensionally analysed by taking the friction against the upper and lower skin layer into consideration. The fibre orientation analysis is carried out, where it is assumed that the fibres are tracked rotating according to the velocity gradient tensor obtained in each element from the numerical results of the flow state analysis. The relationship between the fibre orientation factor and temperature depending material constants are determined and the warp occurring in a product is simulated. The above system was applied to two-dimensional thin plates.In this paper, analysis of the flow state of the three-dimensional structure of plate construction, such as a box was tried out. Two-dimensional analysis was used in each plate and constructed by the coordinate transformation along the edge element. In consideration of the flow state on the edge, the frictional resistance was varied in the element. The result was in good agreement with the experiment.