Electric fields regulate cellular elasticity through intracellular Ca2+ concentrations.

Cellular elasticity is a key factor related to a broad range of physiological and pathological processes. The elasticity of a single cell has thus emerged as a potential biomarker to characterize the cellular state. Both internal and external stimuli affect cellular elasticity, and changes in elasticity can cause alterations in cellular characteristics or function. The application of electric fields (EFs) is a promising method that can be used to change cellular elasticity; however, the mechanisms underlying its effect remain unknown. Here, we demonstrate EFs-induced elasticity changes in human dermal fibroblasts and discuss the underlying mechanism related to actin polymerization. Cellular elasticity increases after EF (50 mV/mm) stimulation, reaching a maximum at 30 min before decreasing between 30 and 120 min. The cellular elasticity under EF stimulation, regardless of stimulation time, is higher than that of the control. F-actin regulates the elasticity of cells through gelsolin activation. We show changes in intracellular Ca2+ caused by EFs, which induced gelsolin activation and F-actin content changes. This result demonstrates a series of processes in which external electrical stimulation conditions regulate cellular elasticity.

Electric field-induced changes in biomechanical properties in human dermal fibroblasts and a human skin equivalent.

PURPOSE: An electric field (EF) can be used to change the mechanical properties of cells and skin tissues. We demonstrate EF-induced elasticity changes in human dermal fibroblasts (HDFs) and a human skin equivalent and identify the underlying principles related to the changes. METHODS: HDFs and human skin equivalent were stimulated with electric fields of 1.0 V/cm. Change in cellular elasticity was determined by using atomic force microscopy. Effects of EF on the biomechanical and chemical properties of a human skin equivalent were analyzed. In cells and tissues, the effects of EF on biomarkers of cellular elasticity were investigated at the gene and protein levels. RESULTS: In HDFs, the cellular elasticity was increased and the expression of biomarkers of cellular elasticity was regulated by the EF. Expression of the collagen protein in the human skin equivalent was changed by EF stimulation; however, changes in density and microstructure of the collagen fibrils were not significant. The viscoelasticity of the human skin equivalent increased in response to EF stimulation, but molecular changes were not observed in collagen. CONCLUSIONS: Elasticity of cells and human skin equivalent can be regulated by electrical stimulation. Especially, the change in cellular elasticity was dependent on cell age.

Microencapsulation of alcohol solvents and high-content actives for efficient transdermal delivery.

The barrier function of the skin in effectively protecting the underlying tissue from the surrounding environment makes it challenging to achieve the efficient transdermal delivery of actives. Herein, we report on alcohol-solvent-encapsulated microcapsules to achieve enhanced skin efficacy. We show that using palm oil as the shell material allows for the microencapsulation of a broad range of alcohol solvents, including ethanol and dipropylene glycol (DPG), as well as on-demand release. Moreover, clinical trials reveal that the high-content actives in microcapsules result in enhanced skin efficacy, and the presence of DPG effectively mediates the transdermal delivery of these actives without causing any skin irritation. We envision that the alcohol-solvent microencapsulation strategy outlined in this work offers new possibilities in cosmetics, food, and drug delivery systems.

Multilamellar ceramide core-structured microvehicles with substantial skin barrier function recovery.

This study introduces a multilamellar ceramide core-structured microvehicle platform for substantial skin barrier function recovery. Our approach essentially focused on fabricating bacterial cellulose nanofiber (BCNF)-enveloped ceramide-rich lipid microparticles (CerMPs) by solidifying BCNF-armored oil-in-water Pickering emulsions. The oil drops consisted of Ceramide NP (a phytosphingosine backbone N-acylated with a saturated stearic acid) and fatty alcohols (FAs) with a designated stoichiometry. The thin BCNF shell layer completely blocked the growth of ceramide molecular crystals from the CerMPs for a long time. The CerMP cores displayed a multilamellar structure wherein the interlayer distance and lateral packing could be manipulated using FAs with different alkyl chain lengths. The CerMPs remarkably lowered the trans-epidermal water loss while restoring the structural integrity of the epidermis in damaged skin. The results obtained herein highlight that the CerMP system provides a practical methodology for developing various types of skin-friendly formulations that can strengthen the skin barrier function.

Skin Penetration Enhancer-Incorporated Lipid Nanovesicles (SPE-LNV) for Skin Brightening and Wrinkle Treatment.

In this work, we utilize skin penetration enhancers (SPEs) such as ceramide and fatty acids in lipid nanovesicles to promote the transdermal delivery of active ingredients. These SPE-incorporated lipid nanovesicles (SPE-LNV) interact with the constituents of skin's outermost stratum corneum (SC) layer, enabling even niacinamide and adenosine with high water solubility to effectively permeate through, leading to enhanced skin efficacy. We demonstrate by both in vitro and in vivo skin permeation studies that the SPE-LNV formulation containing both ceramide and fatty acids (LNV-CF) exhibits deeper penetration depth and faster permeation rate compared to conventional lipid nanovesicles (LNV) without SPE as well as LNV-C with only ceramide. Moreover, in vivo clinical trials were also performed to confirm that LNV-CF most effectively mediates the delivery of niacinamide and adenosine, resulting in a substantial decrease in melanin index as well as skin wrinkle compared to the control groups. We envision that the strategy of incorporating both ceramide and fatty acids in lipid nanovesicles offers a simple and convenient route for the rapid and effective delivery of water-soluble active ingredients across the skin barrier layer.

Highly Sustainable and Completely Amorphous Hierarchical Ceramide Microcapsules for Potential Epidermal Barrier.

As a main component of the stratum corneum, ceramides can construct protective lamellae to provide an epidermal barrier against dehydration or external microorganisms. However, as ceramide molecules can easily form the isolated crystalline phase through self-assembly due to the amphipathic nature of bioactive lipids, the effective incorporation of ceramides into liquid media is the remaining issue for controlled release. Here, we report an unprecedented effective strategy to fabricate a completely amorphous and highly sustainable hierarchical ceramide polymer microcapsule for promising epidermal barrier by using the interpenetrating and cooperative self-construction of conical amphiphiles with a different critical packing parameter. The self-constructed amorphous architecture of ceramides in polymer microcapsule is achieved by the facile doping of conical amphiphiles and subsequent in situ polymerization of shell polymer in the core-shell geometry. It is experimentally revealed that an irregular cooperative packing structure formed by adaptive hydrophobic-hydrophilic interactions of cylindrical ceramides and conical amphiphiles in the confined microcapsule geometry enables a completely amorphous morphology of ceramides to be realized during the spontaneous encapsulation process. Furthermore, this elegant approach affords a highly dispersible and uniform hierarchical amorphous ceramide microcapsule with a greatly enhanced long-term stability compared to conventional crystalline ceramides.

Effective association of ceramide-coassembled lipid nanovehicles with stratum corneum for improved skin barrier function and enhanced skin penetration.

Herein, we report on a ceramide-coassembled lipid nanovehicle (CLNV) system that can enhance the penetration of active ingredients through the skin barrier by taking advantage of molecular associations between ceramide and lipids in the stratum corneum (SC) layer. For this purpose, we fabricated CLNVs consisting of an asymmetric lipid and a cholesterol derivative. They showed excellent long-term dispersion stability without molecular crystallization of ceramide. Upon forming a stable aqueous dispersion, the CLNVs retained their initial vehicle structure even under harsh conditions including high storage temperatures or salinity conditions. From in vitro skin barrier recovery tests, we observed that topical treatment with CLNVs induced the SC to restore its lamellar structure to the same condition as that prior to chemical damage. An in vivo skin penetration study additionally confirmed that skin penetration was enhanced, since the CLNVs were able to effectively interact with the SC layer. From these results, the CLNVs with robust molecular layer endow various applications in wide range applications including transdermal pharmaceutics delivery systems and cosmetics field.