Using Artificial Skin Devices as Skin Replacements: Insights into Superficial Treatment

Artificial skin devices are able to mimic the flexibility and sensory perception abilities of the skin. They have thus garnered attention in the biomedical field as potential skin replacements. This Review delves into issues pertaining to these skin‐deep devices. It first elaborates on the roles that these devices have to fulfill as skin replacements, and identify strategies that are used to achieve such functionality. Following which, a comparison is done between the current state of these skin‐deep devices and that of natural skin. Finally, an outlook on artificial skin devices is presented, which discusses how complementary technologies can create skin enhancements, and what challenges face such devices.     

Mechanism of Transdermal Controlled Nitroglycerin Administration (III) Control of Skin Permeation Rate and Optimization

A mathematical model was developed to correlate the drug permeation rate through the skin with the drug release rate from a matrix-type drug delivery system. Experiments were carried out using hairless mouse abdominal skin mounted on a recently-developed and hydrodynamically well-calibrated Keshary-Chien skin permeation system. A matrix-type drug delivery system was designed to contain different loading doses of nitroglycerin and to study the effect of drug loading variation on the rate of drug release, the rate of skin permeation and the equilibrium concentration of nitroglycerin in the skin.

Results indicated that the stratum corneum plays a significant rate-limiting role in the skin permeation of nitroglycerin across the intact skin, yielding a constant skin permeation profile. The permeation rate across the intact skin was observed to increase with the increase in the drug release flux initially and then levelled off in a hyperbolic fashion. Various constants were obtained from the reciprocal plot of skin permeation rate vs. drug release flux. These constants could be used for the prediction of the skin permeation rate. A very good correlation between the predicted and the observed values of skin permeation rates was observed.

After the stratum corneum was removed by stripping technique, the mechanism and the rate of skin permeation became dominated by the mechanism and the release rate of the delivery system.

A linear correlation was observed between the drug permeation rate through the skin and the equilibrium concentration of drug in the skin. This correlation was observed in both intact and viable skins.     

Influence of epidermal hydration on the friction of human skin against textiles

Friction and shear forces, as well as moisture between the human skin and textiles are critical factors in the formation of skin injuries such as blisters, abrasions and decubitus. This study investigated how epidermal hydration affects the friction between skin and textiles.The friction between the inner forearm and a hospital fabric was measured in the natural skin condition and in different hydration states using a force plate. Eleven males and eleven females rubbed their forearm against the textile on the force plate using defined normal loads and friction movements. Skin hydration and viscoelasticity were assessed by corneometry and the suction chamber method, respectively.In each individual, a highly positive linear correlation was found between skin moisture and friction coefficient (COF). No correlation was observed between moisture and elasticity, as well as between elasticity and friction. Skin viscoelasticity was comparable for women and men. The friction of female skin showed significantly higher moisture sensitivity. COFs increased typically by 43% (women) and 26% (men) when skin hydration varied between very dry and normally moist skin. The COFs between skin and completely wet fabric were more than twofold higher than the values for natural skin rubbed on a dry textile surface.Increasing skin hydration seems to cause gender-specific changes in the mechanical properties and/or surface topography of human skin, leading to skin softening and increased real contact area and adhesion.     

Mechanism of Transdermal Controlled Nitroglycerin Administration (III) Control of Skin Permeation Rate and Optimization

Abstract

A mathematical model was developed to correlate the drug permeation rate through the skin with the drug release rate from a matrix-type drug delivery system. Experiments were carried out using hairless mouse abdominal skin mounted on a recently-developed and hydrodynamically well-calibrated Keshary-Chien skin permeation system. A matrix-type drug delivery system was designed to contain different loading doses of nitroglycerin and to study the effect of drug loading variation on the rate of drug release, the rate of skin permeation and the equilibrium concentration of nitroglycerin in the skin.

Results indicated that the stratum corneum plays a significant rate-limiting role in the skin permeation of nitroglycerin across the intact skin, yielding a constant skin permeation profile. The permeation rate across the intact skin was observed to increase with the increase in the drug release flux initially and then levelled off in a hyperbolic fashion. Various constants were obtained from the reciprocal plot of skin permeation rate vs. drug release flux. These constants could be used for the prediction of the skin permeation rate. A very good correlation between the predicted and the observed values of skin permeation rates was observed.

After the stratum corneum was removed by stripping technique, the mechanism and the rate of skin permeation became dominated by the mechanism and the release rate of the delivery system.

A linear correlation was observed between the drug permeation rate through the skin and the equilibrium concentration of drug in the skin. This correlation was observed in both intact and viable skins.     

Effect of Penetration Enhancers on Transdermal Delivery of Timolol Maleate

In vitro skin permeation of Timolol maleate through human cadaver skin was studied using Franz diffusion cell. The results indicate that the drug penetrates poorly through human cadaver skin. However, skin penetration enhancers such as dimethyl sulfoxide (DMSO), oleic acid (OA) and lauryl chloride (LC) enhanced the permeability of Timolol maleate (TM) through human cadaver skin. The permeation enhancement of drug was maximum by lauryl chloride amongst the three enhancers. Moreover, lauryl chloride increases the permeation of drug through skin with increase in the time of application and concentration on skin. The change in lag time was also observed.     

皮肤对于声音信号响应的研究

为了研究皮肤响应声音信号的理论,构造了测试皮肤响应声音信号的实验环境。通过实验测试了变压器、平面电极与皮肤听“声”之间的频率电压特性曲线,讨论了皮肤响应声音信号的关键部件与皮肤“听”声效果之间的关系,说明了通过声-电转换实现皮肤“听”声的可行性。     

Improvement in Transdermal Bioavailability of Nitroglycerin by Formulation Design

Controlled skin permeation kinetics of nitroglycerin delivered by the three once-a-day transdermal therapeutic systems was recently evaluated and compared using the freshly excised hairless mouse abdominal skin mounted in a finite-dosing Frantz diffusion cell assembly. The kinetics of skin permeation from the conventional ointment formulation was also studied using the same in vitro skin permeation system.

Six experimental formulations of nitroglycerin were developed, aiming to enhance the permeation rate of nitroglycerin through intact skin. The kinetics of skin permeation of nitroglycerin from these experimental formulations was also investigated, using the same in vitro skin permeation system, and compared to the conventional ointment formulation as well as the newly marketed once-a-day transdermal therapeutic systems. Results indicated that the rates of skin permeation can be greatly improved by proper formulation design.     

Improvement in Transdermal Bioavailability of Nitroglycerin by Formulation Design

Abstract

Controlled skin permeation kinetics of nitroglycerin delivered by the three once-a-day transdermal therapeutic systems was recently evaluated and compared using the freshly excised hairless mouse abdominal skin mounted in a finite-dosing Frantz diffusion cell assembly. The kinetics of skin permeation from the conventional ointment formulation was also studied using the same in vitro skin permeation system.

Six experimental formulations of nitroglycerin were developed, aiming to enhance the permeation rate of nitroglycerin through intact skin. The kinetics of skin permeation of nitroglycerin from these experimental formulations was also investigated, using the same in vitro skin permeation system, and compared to the conventional ointment formulation as well as the newly marketed once-a-day transdermal therapeutic systems. Results indicated that the rates of skin permeation can be greatly improved by proper formulation design.     

Effect of Several Electrolyzed Waters on the Skin Permeation of Lidocaine,Benzoic Acid,and Isosorbide Mononitrate

The effects of several electrolyzed waters were evaluated on the permeation of model base, acid and non-ionized compounds, lidocaine (LC), benzoic acid (BA), and isosorbide mononitrate (ISMN), respectively, through excised hairless rat skin. Strong alkaline-electrolyzed reducing water (ERW) enhanced and suppressed the skin permeation of LC and BA, respectively, and it also increased the skin permeation of ISMN, a non-ionized compound. On the contrary, strong acidic electrolyzed oxidizing water (EOW) enhanced BA permeation, whereas suppressing LC permeation. Only a marginal effect was observed on the skin permeation of ISMN by EOW. These marked enhancing effects of ERW on the skin permeation of LC and ISMN were explained by pH partition hypothesis as well as a decrease in skin impedance. The present results strongly support that electrolyzed waters, ERW and EOW, can be used as a new vehicle in topical pharmaceuticals or cosmetics to modify the skin permeation of drugs without severe skin damage.     

The effect of skin penetration enhancers on the transdermal delivery of pyridostigmine bromide

In vitro skin penetration studies of pyridostigmine bromide through human cadaver skin were conducted using a diffusion cell with constant hydrodynamic conditions. The results indicate that the drug penetrates poorly through human cadaver skin. However, skin penetration enhancers such as sodium oleate, sodium lauryl sulfate, n-decyl methyl sulfoxide, and N,N-dimethyldodecylamine-N-oxide substantially enhanced the permeability coefficient of the drug through human cadaver skin. The penetration enhancement of pyridostigmine bromide could be due to increased partitioning of the drug in the skin or due to the decreased tortuosity of the porous pathway in the stratum corneum.     

Bioinspired Composite Microfibers for Skin Adhesion and Signal Amplification of Wearable Sensors

A facile approach is proposed for superior conformation and adhesion of wearable sensors to dry and wet skin. Bioinspired skin‐adhesive films are composed of elastomeric microfibers decorated with conformal and mushroom‐shaped vinylsiloxane tips. Strong skin adhesion is achieved by crosslinking the viscous vinylsiloxane tips directly on the skin surface. Furthermore, composite microfibrillar adhesive films possess a high adhesion strength of 18 kPa due to the excellent shape adaptation of the vinylsiloxane tips to the multiscale roughness of the skin. As a utility of the skin‐adhesive films in wearable‐device applications, they are integrated with wearable strain sensors for respiratory and heart‐rate monitoring. The signal‐to‐noise ratio of the strain sensor is significantly improved to 59.7 because of the considerable signal amplification of microfibrillar skin‐adhesive films.     

Automatic skin segmentation and tracking in sign language recognition

Skin segmentation and tracking play an important role in sign language recognition. A framework for segmenting and tracking skin objects from signing videos is described. It mainly consists of two parts: a skin colour model and a skin object tracking system. The skin colour model is first built based on the combination of support vector machine active learning and region segmentation. Then, the obtained skin colour model is integrated with the motion and position information to perform segmentation and tracking. The tracking system is able to predict occlusions among any of the skin objects using a Kalman filter (KF). Moreover, the skin colour model can be updated with the help of tracking to handle illumination variation. Experimental evaluations using real-world gesture videos and comparison with other existing algorithms demonstrate the effectiveness of the proposed work.     

X-ray imaging and the skin: radiation biology, patient dosimetry and observed effects

A wide variety of radiation-induced deterministic skin effects have been observed after X-ray guided interventions ranging from mild effects, such as transient erythema or temporary epilation, to severe effects, such as desquamation and necrosis. Radiation biologists have identified, in addition to absorbed dose to the skin, other factors that strongly influence the type and severity of a skin reaction, including exposure-related factors (dose rate, fractionation, the size of the exposed area and its site), biological factors (age, oxygen status, capillary density, hormonal status and genetic factors) and ethnic differences. A peak entrance skin dose of 2 Gy is an arbitrary, but pragmatic, threshold for radiation-induced skin effects after X-ray guided interventions. Transient skin injury originating in the epidermis is not expected in the average patient population at peak entrance skin doses up to 6 Gy. Serious skin effects are not likely to occur in clinical practice when optimised X-ray equipment is used in combination with good techniques for fluoroscopy and imaging. However, this might not be true for patients with biological factors that are associated with an increased sensitivity for radiation-induced skin reactions.     

The effect of skin penetration enhancers on the transdermal delivery of pyridostigmine bromide

Abstract

In vitro skin penetration studies of pyridostigmine bromide through human cadaver skin were conducted using a diffusion cell with constant hydrodynamic conditions. The results indicate that the drug penetrates poorly through human cadaver skin. However, skin penetration enhancers such as sodium oleate, sodium lauryl sulfate, n-decyl methyl sulfoxide, and N,N-dimethyldodecylamine-N-oxide substantially enhanced the permeability coefficient of the drug through human cadaver skin. The penetration enhancement of pyridostigmine bromide could be due to increased partitioning of the drug in the skin or due to the decreased tortuosity of the porous pathway in the stratum corneum.     

Formulation study of topically applied O/W lotion containing vitamin D3 derivative, focusing on skin permeability of the drug

Permeation of 22-oxacalcitriol-1α, 25-dihydroxyvitamin D(3) (OCT) through excited hairless mouse skin was determined after application of OCT as solutions and O/W lotions consisted of different polarities of solvents: medium-chain fatty acid triglyceride (MCT), myristate isopropyl (IPM), 1,3-butylene glycol (1,3-BG), and propylene glycol (PG). OCT concentration in skin was also followed after applying these formulations. A two-layer diffusion model was composed to analyze dermatopharmacokinetic profiles of OCT for each vehicle. In the OCT solutions, skin permeation profile of OCT differed depending on solvent polarity. The O/W lotion with a high MCT content led to a low amount of OCT in skin. On the other hand, the O/W lotion with a high 1,3-BG content led to a high amount of OCT in skin. This dermatopharmacokinetic analysis indicated that addition of MCT to the formulation decreases the skin/vehicle partition coefficient of OCT and increases the diffusion coefficient of OCT in skin. However, the opposite effects on these two parameters were found in the case of 1,3-BG. Thus, skin permeability of OCT differed depending on the solvents used in the formulation. These results indicate that skin permeability of OCT is influenced by the physicochemical properties (i.e. polarity) of OCT, solvent, and skin. Our findings on the solvent effects of the skin permeability of OCT are thus useful for designing topical drug formulation, especially in aiming for bioequivalent dosage formulas.     

非均质表皮层径向双层承压井流数学模型的半解析解

考虑表皮层和未扰动承压层的非均质性、各向异性以及竖向越流补给作用,建立了径向双层承压三维井流的数学模型,采用Laplace变换和矩阵理论求得表皮层和未扰动承压层的水头降以及井壁流量的半解析解.应用所求解编制计算程序,分析了表皮层沿竖向随机变化的渗透性对承压层井流的影响,结果表明:表皮层非均质变化形态决定了表皮层内和其附近处的水头降以及井壁流量的竖向分布规律,表皮层对承压层渗流产生的影响范围与承压层的竖向渗透系数大小有关;改善井周岩土介质渗透性或增大"负表皮层"厚度可提高抽水井产量;表皮层径向渗透系数较小时,承压层的水头降幅度主要取决于承压层径向渗透系数的大小,而当表皮层径向渗透系数较大时,承压层径向渗透系数和竖向渗透系数均对承压层水头降有较大影响.     

In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR

Ultraviolet radiation (UVR) has widespread effects on the biology and integrity of the skin barrier. Research on the mechanisms that drive these changes, as well as their effect on skin barrier function, has been ongoing since the 1980s. However, no studies have examined the impact of UVR on nanoparticle skin penetration. Nanoparticles (NP) are commonly used in sunscreens and other cosmetics, and since consumer use of sunscreen is often applied to sun damaged skin, the effect of UVR on NP skin penetration is a concern due to potential toxicity. In this study, we investigate NP skin penetration by employing an in vivo semiconductor quantum dot nanoparticle (QD) model system. This model system improves NP imaging capabilities and provides additional primary interest due to widespread and expanding use of QD in research applications and manufacturing. In our experiments, carboxylated QD were applied to the skin of SKH-1 mice in a glycerol vehicle with and without UVR exposure. The skin collection and penetration patterns were evaluated 8 and 24 h after QD application using tissue histology, confocal microscopy, and transmission electron microscopy (TEM) with EDAX analysis. Low levels of penetration were seen in both the non-UVR exposed mice and the UVR exposed mice. Qualitatively higher levels of penetration were observable in the UVR exposed mice. These results are the first for in vivo QD skin penetration, and provide important insight into the ability of QD to penetrate intact and UVR compromised skin barrier. Our findings raise concern that NP of similar size and surface chemistry, such as metal oxide NP found in sunscreens, may also penetrate UV damaged skin.     

Evaluation of salicylic acid fatty ester prodrugs for UV protection

The purpose of this study was to investigate the physicochemical properties and in vitro evaluation of fatty ester prodrugs of salicylic acid for ultraviolet (UV) protection. The physicochemical properties such as lipophilicity, chemical stability and enzymatic hydrolysis were investigated with the following fatty ester prodrugs of salicylic acid: octanoyl (C8SA), nonanoyl (C9SA), decanoyl (C10SA), lauroyl (C12SA), myristoyl (C14SA) and palmitoyl oxysalicylate (C16SA). Furthermore, their skin permeation and accumulation were evaluated using a combination of common permeation enhancing techniques such as the use of a lipophilic receptor solution, removal of stratum corneum and delipidization of skin. Their k' values were proportional to the degree of carbon-carbon saturation in the side chain. All these fatty esters were highly stable in 2-propanol, acetonitrile and glycerin, but unstable in methanol and ethanol. They were relatively unstable in liver and skin homogenates. In particular, C16SA was mostly hydrolyzed to its parent compound in hairless mouse liver and skin homogenates, suggesting that it might be converted to salicylic acid after its topical administration. In the skin permeation and accumulation study, C16SA showed the poorest permeation in all skins, suggesting that it could not be permeated in the skin. Furthermore, C14SA and C16SA were less accumulated in delipidized skin compared with normal skin or stripped skin, suggesting that these esters had relatively strong affinities for lipids compared with the other prodrugs in the skin. C16SA showed significantly higher dermal accumulation in all skins compared with its parent salicylic acid. Thus, the palmitoyl oxysalicylate (C16SA) might be a potential candidate for UV protection due to its absence of skin permeation, smaller uptake in the lipid phase and relatively lower skin accumulation.     

Topical Delivery of Fluconazole: In Vitro Skin Penetration and Permeation Using Emulsions as Dosage Forms

ABSTRACT

We investigated in vitro skin penetration and permeation of fluconazole from emulsions containing different penetration enhancers. Fluconazole permeation was high (15–65% of the applied dose) across hairless mouse skin and low (8–9%) across pig ear skin. Permeation across mice skin from a formulation containing propyleneglycol and isopropyl myristate was significantly higher than that observed with the paraffin oil and propyleneglycol or Transcutol® emulsions. With pig skin, the paraffin oil or isopropyl myristate and propyleneglycol emulsions showed similar skin permeation and penetration. However, these emulsions provided epidermal concentrations higher than the minimal inhibitory concentrations for most dermatophytes.     

Topical delivery of fluconazole: in vitro skin penetration and permeation using emulsions as dosage forms

We investigated in vitro skin penetration and permeation of fluconazole from emulsions containing different penetration enhancers. Fluconazole permeation was high (15-65% of the applied dose) across hairless mouse skin and low (8-9%) across pig ear skin. Permeation across mice skin from a formulation containing propyleneglycol and isopropyl myristate was significantly higher than that observed with the paraffin oil and propyleneglycol or Transcutol® emulsions. With pig skin, the paraffin oil or isopropyl myristate and propyleneglycol emulsions showed similar skin permeation and penetration. However, these emulsions provided epidermal concentrations higher than the minimal inhibitory concentrations for most dermatophytes.