Depth profiling of epidermal hydration inducing improvement of skin roughness and elasticity: in vivo study by confocal Raman spectroscopy.

INTRODUCTION: Skin hydration in the stratum corneum plays an important role in skin condition, and skin efficacy properties are influenced by its hydration level. However, few studies have identified the correlation between changes in skin hydration content and skin characteristics by skin depth level. AIMS: This study aims to determine how changes in skin hydration at specific depth levels affect skin condition by long-term tracking changes in hydration of stratum corneum and viable epidermis after usage of moisturizer. METHODS: Ten volunteers were recruited and subjected to in vivo confocal Raman spectroscopy to perform water content profiling at skin depths of up to 52 µm. Mechanical properties of skin were measured using Cutometer and Antera 3D. Skin-elasticity and roughness values observed before and after 15 days of moisturizing emulsion use were compared to demonstrate the correlation between observed changes in skin efficacy parameters and skin water content at specific depths. RESULTS: Significant increase in relative water content at specific depths was observed in this study. Among mechanical properties of skin, only R4, R6, and R8 parameters demonstrated significant changes. Additionally, rates of change in values of the R6 and R8 parameters revealed a high correlation with water content changes at viable epidermis depths below the stratum corneum. On the other hand, skin roughness parameter showed a correlation with water content changes at the outermost layer of stratum corneum. CONCLUSION: Results of this study indicate that skin elasticity is influenced by its hydration level at viable epidermis depths and skin roughness at stratum corneum each. This suggests that monitoring depth profiles of water content using in vivo confocal Raman spectroscopy provides a breakthrough in tracking the skin efficacy effect of topically applied substances.

Mechanical Impedance of Rat Glabrous Skin and Its Relation With Skin Morphometry.

The mechanical impedance of intact and epidermis-peeled rat glabrous skin was studied at two sites (digit and sole) and at two frequencies (40 Hz and 250 Hz). The thicknesses of skin layers at the corresponding regions were measured histologically from intact- and peeled-skin samples in every subject. Compared to intact sole skin, digital rat skin has thicker layers and higher mechanical resistance, and it is less stiff. The resistance of the skin significantly decreased after epidermal peeling at both the digit and the sole. Furthermore, peeling caused the reactance to become positive due to inertial effects. As the frequency was increased from 40 to 250 Hz, the resistance and stiffness also increased for the intact skin, while the peeled skin showed less frictional (i.e., resistance) but more inertial (i.e., positive reactance) effects. We estimated the mechanical properties of epidermis and dermis with lumped-element models developed for both intact and peeled conditions. The models predicted that dermis has higher mass, lower stiffness, and lower resistance compared to epidermis, similar to the experimental impedance results obtained in the peeled condition which consisted mostly of dermis. The overall impedance was simulated more successfully at 40 Hz. When both frequencies are considered, the models produced consistent results for resistance in both conditions. The results imply that most of the model parameters should be frequency-dependent and suggest that mechanical properties of epidermis can be related to its thickness. These findings may help in designing artificial skin for neuroprosthetic limbs.

Transfersomes improved delivery of ascorbic palmitate into the viable epidermis for enhanced treatment of melasma.

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.

Comparative analysis of intrinsic skin aging between Caucasian and Asian subjects by slide-free in vivo harmonic generation microscopy.

Phenotypical and functional differences in the intrinsic skin aging process of individuals between Caucasians and Asians have generated considerable interest in dermatology and cosmetic industry. Most of the studies focused on the stratum corneum, and in some other studies inter-individual differences overwhelms the racial difference. None of the studies comparatively analyzes the difference from the histopathological point of view. Here we report our harmonic generation microscopy study to analyze the difference of intrinsic aging between Caucasian and Asian skin from a histopathological point of view. As a result, the cellular and nuclear areas of basal cells in Caucasian subjects were found to increase at the same rate as the Asian subjects, ideal for scoring age. The maximum thickness of the viable epidermis, the dermal papilla (DP) volume per unit area and the depth of the DP zone in Caucasians were found to decrease at faster rates than those in Asians.

Mechanism study on ion-pair complexes controlling skin permeability: Effect of ion-pair dissociation in the viable epidermis on transdermal permeation of bisoprolol.

Though ion-pair strategy has been widely used in transdermal drug delivery system, knowledge about the molecular mechanisms involved in the skin permeation processes of ion-pair complexes is still limited. In the present study, a homologous series of fatty acids were chosen to form model ion-pair complexes with bisoprolol (BSP) to rule out the influence of functional groups on polar surface area, stability and other physicochemical properties of ion-pair complexes. The ion-pair complexes were characterized by FTIR, thermal analysis, and 1H NMR. The skin permeability of BSP as well as its ion-pair complexes was investigated by in vitro skin permeation experiments then visualized by CLSM. The skin permeability coefficient (kp) of BSP ion-pair complex was negatively related to its n-octanol/water apparent partition coefficient (P'o/w) in the hydrophobic vehicle caprylic/capric triglyceride, (log kp=-1.657-1.229 log P'o/w), suggesting that the instability of ion-pair complexes due to their dissociation in the viable epidermis (VED) played an important role in controlling the skin permeability of BSP, which was further proved by 1H NMR and molecular docking. These findings broadened our understanding about the molecular mechanisms involved in the skin permeation processes of ion-pair complexes.

Ex vivo Skin Permeation Evaluation of An Innovative Transdermal Vehicle Using Nimesulide and Piroxicam as Model Drugs.

BACKGROUND: The transdermal dosage forms presented a limited usage for a long time, for it was believed that the stratum corneum, the outermost layer of epidermis, made it impracticable the permeation of medications through the skin. Studies exploring this area came up with strategies to overcome this barrier; for example, creating a transdermal vehicle to facilitate the drug absorption. OBJECTIVE: This study aimed to evaluate a new transdermal vehicle through the comparison of its permeation profile and the profile of commercial products, using nimesulide and piroxicam, non steroidal anti-inflammatory drugs. METHODS: Four different products were evaluated: nimesulide and piroxicam compounded with the new vehicle (emulsion) and commercial nimesulide and piroxicam gels. Ex vivo permeation experiments using Franz-type diffusion cell equipment were conducted, using human skin as membrane. For evaluation of permeated active pharmaceutical ingredients concentrations, we performed quantification from the receptor solution, stratum corneum and viable epidermis + dermis, through high-performance liquid chromatography analyses. RESULTS: The new vehicle promoted increased permeation of active pharmaceutical ingredients through the viable epidermis and dermis, when compared to commercial products, but the stratum corrneum continued to keep the highest retention. CONCLUSION: The innovative vehicle was capable of enhancing the transdermal absorption of active pharmaceutical ingredients from the compounded formulations, thus, demonstrating the capability thereof to improve the permeability of active pharmaceutical ingredients by transdermal use.