Skin Research Articles

P33 Skinvaders: gamification of the skin barrier to engage school-age children in the biology of the skin

Abstract Introduction and aims Public engagement is an essential part of research design. It provides opportunities for both scientists and the public to learn, and inspires the next generation of researchers. We are fortunate to have a public engagement centre within our institution, which contains digital games, an established and effective way to engage children. We developed a new game for school-age children to engage them in the Paediatric Human Cell Atlas, a collaborative project that aims to map single-cell profiles and spatial characterization of gene expression across human tissues and organs throughout development. Our aim was to develop a game that involved different skin cell types, variation in skin colour and common skin disorders. Methods Initial steps included brainstorming with our public engagement staff about content and then developing a lay summary and agreeing on the following key themes: the skin as a barrier, the cells of the skin, and eczema, a common skin disorder. The game was based on the arcade game Breakout. It features a customizable paddle representing the skin, demonstrating how changes in quantities of different skin components can change appearance/function (e.g. melanin production, adipocytes, hair follicles), which players must move across the screen to keep pathogens and allergens out and keep water and protein in. In the last level, barrier function is impaired by eczema and the children can catch cream to repair the barrier. Results The game was developed for our public engagement centre where it has undergone testing by target audiences. Conclusions We have created a game as an innovative way to engage and educate paediatric communities in our research. It was challenging to simplify scientific content for use in a game while staying true to the scientific concepts. We will increase reach by adapting the game for desktop and app-based formats.

Antioxidant and Anti-Inflammatory Properties of Hydrolyzed Royal Jelly Peptide in Human Dermal Fibroblasts: Implications for Skin Health and Care Applications.

Hydrolyzed royal jelly peptide (RJP) has garnered attention for its health-promoting functions. However, the potential applications of RJP in skincare have not been fully explored. In this study, we prepared RJP through the enzymatic hydrolysis of royal jelly protein with trypsin and investigated its antioxidant and anti-inflammatory properties on primary human dermal fibroblasts (HDFs). Our results demonstrate that RJP effectively inhibits oxidative damage induced by H2O2 and lipid peroxidation triggered by AAPH and t-BuOOH in HDFs. This effect may be attributed to the ability of RJP to enhance the level of glutathione and the activities of catalase and glutathione peroxidase 4, as well as its excellent iron chelating capacity. Furthermore, RJP modulates the NLRP3 inflammasome-mediated inflammatory response in HDFs, suppressing the mRNA expressions of NLRP3 and IL-1β in the primer stage induced by LPS and the release of mature IL-1β induced by ATP, monosodium urate, or nigericin in the activation stage. RJP also represses the expressions of COX2 and iNOS induced by LPS. Finally, we reveal that RJP exhibits superior antioxidant and anti-inflammatory properties over unhydrolyzed royal jelly protein. These findings suggest that RJP exerts protective effects on skin cells through antioxidative and anti-inflammatory mechanisms, indicating its promise for potential therapeutic avenues for managing oxidative stress and inflammation-related skin disorders.

Dermatologic manifestations of hereditary hemochromatosis: A systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder leading to excessive iron absorption, impacting multiple organs, notably the skin, nails and mucosae. The objective of this study is to elucidate the dermatologic manifestations, associated symptoms, pathophysiology and management recommendations of HH. We searched five primary databases (PubMed, Embase, Cochrane Library, Scopus and Web of Science) up to April 2023. Non-English articles were included to minimize language bias. The studies were evaluated using Oxford Centre for Evidence-based Medicine standards, with adherence to PRISMA guidelines. Inaccessible articles were directly sourced from authors. Out of the initial 1582 publications from 1904 to 2023, 22 studies (19 in English, 2 in French and 1 in German) were selected. Most reports were from the USA, UK and France and were predominantly case reports, covering 148 patients with skin symptoms related to hereditary hemochromatosis. We collected data on the cutaneous findings and, when available, their histopathological features. The current study highlights the scope, variety and traits of dermatologic symptoms in hereditary hemochromatosis, pinpointing research gaps and areas for future exploration. Our review accentuates the diverse dermatological manifestations of hereditary hemochromatosis, notably hyperpigmentation, hypertrichosis and resistant pruritus, often linked to excessive iron deposition and subsequent impairment of skin cell function. We also found controversial evidence indicating that skin cancers seem to be associated with hereditary hemochromatosis. Porphyria cutanea tarda and hereditary hemochromatosis were frequently reported together. Given hereditary hemochromatosis's genetic nature, early identification in one individual can substantially guide familial care and preemptive interventions. Clinicians should prioritize hereditary hemochromatosis as a differential when patients present with specific dermatological symptoms, especially in sun-exposed regions. A rigorous assessment ensures accurate diagnosis, facilitating optimal management for both the patient and their family.

Subminute thermal damage to cell types present in the skin

Introduction Psoriasis is characterized by an increase in the proliferation of keratinocytes and nerve fiber activity, contributing to the typical skin lesions. Pulsed Dye Laser (PDL) treatment is effective for the treatment of psoriatic lesions but its mechanism remains unclear. One hypothesis is that PDL causes thermal damage by the diffusion of heat to neighboring structures in lesional skin. There is limited information on the thermal sensitivity of these neighboring skin cells when exposed to hyperthermia for durations lasting less than a minute. Our study aimed to investigate the cell-specific responses to heat using sub-minute exposure times and moderate to ablative hyperthermia. Materials and Methods Cultured human endothelial cells, smooth muscle cells, neuronal cells, and keratinocytes were exposed to various time (2–20 sec) and temperature (45–70 °C) combinations. Cell viability was assessed by measuring intracellular ATP content 24 h after thermal exposure and this data was used to calculate fit parameters for the Arrhenius model and CEM43 calculations. Results Our results show significant differences in cell survival between cell types (p < 0.0001). Especially within the range of 50–60 °C, survival of neuronal cells and keratinocytes was significantly less than that of endothelial and smooth muscle cells. No statistically significant difference was found in the lethal dose (LT50) of thermal energy between neuronal cells and keratinocytes. However, CEM43 calculations showed significant differences between all four cell types. Conclusion The results imply that there is a cell-type-dependent sensitivity to thermal damage which suggests that neuronal cells and keratinocytes are particularly susceptible to diffusing heat from laser treatment. Damage to these cells may aid in modulating the neuro-inflammatory pathways in psoriasis. These data provide insight into the potential mechanisms of PDL therapy for psoriasis and advance our understanding of how thermal effects may play a role in its effectiveness.

A novel skin cancer detection model using modified finch deep CNN classifier model

Skin cancer is one of the most life-threatening diseases caused by the abnormal growth of the skin cells, when exposed to ultraviolet radiation. Early detection seems to be more crucial for reducing aberrant cell proliferation because the mortality rate is rapidly rising. Although multiple researches are available based on the skin cancer detection, there still exists challenges in improving the accuracy, reducing the computational time and so on. In this research, a novel skin cancer detection is performed using a modified falcon finch deep Convolutional neural network classifier (Modified Falcon finch deep CNN) that efficiently detects the disease with higher efficiency. The usage of modified falcon finch deep CNN classifier effectively analyzed the information relevant to the skin cancer and the errors are also minimized. The inclusion of the falcon finch optimization in the deep CNN classifier is necessary for efficient parameter tuning. This tuning enhanced the robustness and boosted the convergence of the classifier that detects the skin cancer in less stipulated time. The modified falcon finch deep CNN classifier achieved accuracy, sensitivity, and specificity values of 93.59%, 92.14%, and 95.22% regarding k-fold and 96.52%, 96.69%, and 96.54% regarding training percentage, proving more effective than literary works.

MRNA Splicing of UL44 and Secretion of Alphaherpesvirinae Glycoprotein C (gC) Is Conserved among the Mardiviruses.

Marek's disease (MD), caused by gallid alphaherpesvirus 2 (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas throughout the body. Vaccine strains used against MD include gallid alphaherpesvirus 3 (GaAHV3), a non-oncogenic chicken alphaherpesvirus homologous to MDV, and homologous meleagrid alphaherpesvirus 1 (MeAHV1) or turkey herpesvirus (HVT). Previous work has shown most of the MDV gC produced during in vitro passage is secreted into the media of infected cells although the predicted protein contains a transmembrane domain. We formerly identified two alternatively spliced gC mRNAs that are secreted during MDV replication in vitro, termed gC104 and gC145 based on the size of the intron removed for each UL44 (gC) transcript. Since gC is conserved within the Alphaherpesvirinae subfamily, we hypothesized GaAHV3 (strain 301B/1) and HVT also secrete gC due to mRNA splicing. To address this, we collected media from 301B/1- and HVT-infected cell cultures and used Western blot analyses and determined that both 301B/1 and HVT produced secreted gC. Next, we extracted RNAs from 301B/1- and HVT-infected cell cultures and chicken feather follicle epithelial (FFE) skin cells. RT-PCR analyses confirmed one splicing variant for 301B/1 gC (gC104) and two variants for HVT gC (gC104 and gC145). Interestingly, the splicing between all three viruses was remarkably conserved. Further analysis of predicted and validated mRNA splicing donor, branch point (BP), and acceptor sites suggested single nucleotide polymorphisms (SNPs) within the 301B/1 UL44 transcript sequence resulted in no gC145 being produced. However, modification of the 301B/1 gC145 donor, BP, and acceptor sites to the MDV UL44 sequences did not result in gC145 mRNA splice variant, suggesting mRNA splicing is more complex than originally hypothesized. In all, our results show that mRNA splicing of avian herpesviruses is conserved and this information may be important in developing the next generation of MD vaccines or therapies to block transmission.

Ammonia Detection by Electronic Noses for a Safer Work Environment

Providing employees with proper work conditions should be one of the main concerns of any employer. Even so, in many cases, work shifts chronically expose the workers to a wide range of potentially harmful compounds, such as ammonia. Ammonia has been present in the composition of products commonly used in a wide range of industries, namely production in lines, and also laboratories, schools, hospitals, and others. Chronic exposure to ammonia can yield several diseases, such as irritation and pruritus, as well as inflammation of ocular, cutaneous, and respiratory tissues. In more extreme cases, exposure to ammonia is also related to dyspnea, progressive cyanosis, and pulmonary edema. As such, the use of ammonia needs to be properly regulated and monitored to ensure safer work environments. The Occupational Safety and Health Administration and the European Agency for Safety and Health at Work have already commissioned regulations on the acceptable limits of exposure to ammonia. Nevertheless, the monitoring of ammonia gas is still not normalized because appropriate sensors can be difficult to find as commercially available products. To help promote promising methods of developing ammonia sensors, this work will compile and compare the results published so far.

The selective cytotoxicity effect of biosynthesized zinc oxide nanoparticles using honey

This work aims to produce biosynthesized zinc oxide nanoparticles using honey (Ho-ZnO-NPs). First, the process of characterization was completed using different techniques, including the color changing to light brown, Zeta-potential that shows a sharp peak at − 5.08 mV, Energy Dispersive X-ray (EDX), which represents the high percentage of Zinc (57.36 %), oxygen (35.03 %) and carbon (7.62 %), Transmission and Scanning Electron Microscopy (TEM and SEM) and X-ray Diffraction (XRD) analysis that illustrate the spherical and hexagonal structure. Then, the cytotoxicity activity was studied using an MTT assay on three cancer cell lines (MCF-7, HepG2, and A431) and an HSF normal cell line. Furthermore, the prepared nanoparticles Ho-ZnO-NPs show that the different IC50 are 118.1, 49.5, and 751.7 µg/mL for MCF-7, HepG2, and A431, respectively. In addition, IC50 is 1.47 mg/mL for HSF. In conclusion, the study reveals that the biosynthesized Ho-ZnO-NPs have higher anticancer activity against HepG2, plus their safety against normal skin cells.

Sensory neurons increase keratinocyte proliferation through CGRP release in a tissue engineered in vitro model of innervation in psoriasis

Skin denervation has been shown to cause remission of psoriatic lesions in patients, which can reappear if reinnervation occurs. This effect can be induced by the activation of dendritic cells through sensory innervation. However, a direct effect of nerves on the proliferation of keratinocytes involved in the formation of psoriatic plaques has not been investigated. We developed, by tissue engineering, a model of psoriatic skin made of patient skin cells that showed increased keratinocyte proliferation and epidermal thickness compared to healthy controls. When this model was treated with CGRP, a neuropeptide released by sensory neurons, an increased keratinocyte proliferation was observed in the psoriatic skin model, but not in the control. When a sensory nerve network was incorporated in the psoriatic model and treated with capsaicin to induce neuropeptide release, an increase of keratinocyte proliferation was confirmed, which was blocked by a CGRP antagonist while no difference was noticed in the innervated healthy control. We showed that sensory neurons can participate directly to keratinocyte hyperproliferation in the formation of psoriatic lesions through the release of CGRP, independently of the immune system. Our unique tissue-engineered innervated psoriatic skin model could be a valuable tool to better understand the mechanism by which nerves may modulate psoriatic lesion formation in humans. Statement of significanceThis study shows that keratinocytes extracted from patients’ psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release.

Development of a facile, versatile and scalable fabrication approach of solid, coated, and dissolving microneedle devices for transdermal drug delivery applications

Nowadays, microneedles as novel transdermal delivery systems are interested in scientists for biomedical applications. This work aims to present a Cascade Microneedle Molding Technique (CMMT) for the reusable fabrication of polydimethylsiloxane (PDMS) molds to produce microneedle devices. To produce a positive master mold from epoxy resin, a negative PDMS mold was first fabricated. PDMS can be molded, and microneedles can be fabricated using this epoxy mold in a scalable and cost-effective manner. These molds were used to manufacture solid, coated, and dissolving microneedles, which were characterized comprehensively. Microneedle morphology and geometry were evaluated using Scanning Electron Microscopy (SEM). The mechanical integrity and ability to insert the microneedle device into the skin were assessed using compression strength analysis and force-displacement measurements. Drug penetration through animal skin was evaluated for Rhodamine B (RhB) loaded microneedles. The depth of needle insertion was also visualized using histological analysis while the spatial distribution of released cargo was determined by using confocal microscopy. Taken together, CMMT offers a simple, rapid, cost-effective, and scalable method for mass-producing microneedles with remarkable properties compared to direct 3D printing or laser ablation.

Rice bran oil supports robust growth of the commensal fungus Malassezia

Malassezia are lipophilic budding yeasts that thrive on natural lipid sources. They are found on the skin, scalp, and upper back of humans and other warm-blooded animals, due to the high sebaceous gland activity in these regions that support their growth. They generally thrive as commensals and, upon certain not-so-well-defined conditions, transform into pathogenic states, giving rise to dermatological diseases and, at times, systemic infections. The studies for identifying the role of Malassezia in causing disease are severely hampered due to the lack of suitable growth media. Because of the challenges associated with isolation, there have been cases reported of undetectable fungal sepsis and often misdiagnosis for the same reason. The media routinely used for culturing yeast is supplemented with lipids. This study aimed to show that an inexpensive oil supplement like rice bran can support the growth of Malassezia, and SDA media supplemented with rice bran oil gave commendable growth of the budding yeast, better than the traditionally used olive oil-supplemented media. Therefore, rice bran oil can be used as a lipid supplement in the culture medium for the isolation, and maintenance of lipophilic yeasts. Our study again signifies the importance of media in microbiological research and stresses the need to develop better growth substrates for difficult-to-culture organisms like Malassezia and this will aid in molecular taxonomy, species characterization and phylogenetic studies.

Tuning multiple enzyme-like activities by metal doping for identification and quantitation of antioxidants in cosmetics

Inspired by the hydrolysis behaviors of skin cells, we exquisitely designed and synthesized a class of hydrolase mimics to develop an analytical method that can both identify and quantity antioxidant components in skin-whitening cosmetics, including ascorbic acid (AA) and its glycoside and phosphate derivatives. A series of ultra-thin Cu1-xMnxO2 or Fe1-yMnyO2 with rich acid-base pairs were prepared via chemical deposition and in-situ CuI/FeII self-assembly. H218O and D216O isotopic labeling studies and density function theory (DFT) calculations were adopted to analyze the cleaving sites of ascorbyl phosphate (AAL)/ascorbyl glucoside (AAP) and confirm that H2O was involved in the new bonds. In-situ DRIFT NH3-IR and −TPD further confirmed that the Fe- or Cu-substitution could increase the quantity and strength of Brønsted and Lewis acid sites. A cascade catalytic fluorescence sensor was designed for selective recognition or quantification of AA and its derivatives, which presents ultra-high-precision (≤2.5 %), stability, and selectivity in testing the target ingredients of five cosmetics from the market. Our nanozymes exhibit higher catalytic efficiency of 17.1 s−1 for AA, 8.42 s−1 for AAL, and 3.32 s−1 for AAP, which are 5.6 ∼ 32.8-fold higher than those of their mimic proteases. This work provides a controllable methodology to design hydrolytic nanozymes, which sheds light on biomimetic engineering and paves the way for breakthroughs in cosmetics industrial applications in the future.

A new G3BP1-GFP reporter system for assessing skin toxicity by real-time monitoring of stress granules in vitro

The skin, the organ with the largest surface area in the body, is the most susceptible to chemical exposure from the external environment. In this study, we aimed to establish an in vitro skin toxicity monitoring system that utilizes the mechanism of stress granule (SG) formation induced by various cellular stresses. In HaCaT cells, a keratinocyte cell line that comprises the human skin, a green fluorescent protein (GFP) was knocked in at the C-terminal genomic locus of Ras GTPase-activating protein-binding protein 1 (G3BP1), a representative component of SGs. The G3BP1-GFP knock-in HaCaT cells and wild-type (WT) HaCaT cells formed SGs containing G3BP1-GFP upon exposure to arsenite and household chemicals, such as bisphenol A (BPA) and benzalkonium chloride (BAC), in real-time. In addition, the exposure of G3BP1-GFP knock-in HaCaT cells to BPA and BAC promoted the phosphorylation of eukaryotic initiation factor 2 alpha and protein kinase R-like endoplasmic reticulum kinase, which are cell signaling factors involved in SG formation, similar to WT HaCaT cells. In conclusion, this novel G3BP1-GFP knock-in human skin cell system can monitor SG formation in real-time and be utilized to assess skin toxicity to various substances.

Radiofrequency Treatment Attenuates Age-Related Changes in Dermal-Epidermal Junctions of Animal Skin.

The dermal-epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-β production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-β, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-β and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-β. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.

Dress protective potential of naturally green-colored domestic silk against ultraviolet-induced skin cell damage

Naturally green-colored domestic silk demonstrates remarkable antioxidant activity due to the presence of intrinsic antioxidant and pigmented substance flavonoids. Oxidative damage is one of the main causes of sun-induced skin damage. To investigate the potential protective effect of naturally green-colored domestic silk on skin cells against ultraviolet damage, the antioxidant was extracted and analyzed. An in vitro experiment which involves introducing ultraviolet damage to the human keratinocyte HaCaT cell line was used for the research. By adding the extract into HaCaT culture medium and then subjecting to ultraviolet irradiation, the data evidently showed that the cell apoptosis and growth inhibition of HaCaT were alleviated, indicating the protective effect of the extract to the HaCaT cell against ultraviolet damage. Meanwhile, a large number of the surviving damaged cells stagnated in the diploid (2n) phase, which is the main phase of gene repair during the whole cell cycle. The survival and repair of damaged cells also produced fewer gene fragments caused by ultraviolet damage. The detected reduction of reactive oxygen species and malondialdehyde induced by ultraviolet irradiation in HaCaT confirmed that the antioxidant extract from green silk cocoons does have intracellular and extracellular antioxidant effects. These findings suggest that naturally green silk has the potential to be utilized as a functional textile material for skin sunscreen products, and its extract can be further developed as a source of antioxidants in medical and safety health applications.

Quercetin loaded polymeric dissolving microarray patches: fabrication, characterisation and evaluation

AbstractQuercetin, a natural compound, shows promising potential in wound healing by reducing fibrosis, limiting scar formation, and boosting fibroblast proliferation. However, its effectiveness is hindered by poor solubility, resulting in low bioavailability and necessitating high doses for therapeutic efficacy. This study presents a novel approach, fabricating quercetin-loaded microarray patches (MAPs) using widely employed solubility enhancement strategies. Fabricated MAPs exhibited favourable mechanical strength and could be inserted into excised porcine skin to a depth of 650 μm. Furthermore, formulations containing Soluplus® significantly increased the drug loading capacity, achieving up to 2.5 mg per patch and complete dissolution within an hour of application on excised porcine skin. In vitro studies on full-thickness neonatal porcine skin demonstrated that Soluplus®-enhanced MAPs effectively delivered quercetin across various skin layers, achieving a delivery efficiency exceeding 80% over 24 h. Additionally, these prototype MAPs displayed anti-inflammatory properties and demonstrated biocompatibility with human keratinocyte skin cells. Therefore, quercetin-loaded MAPs employing Soluplus® as a solubility enhancer present a promising alternative strategy for wound healing and anti-inflammatory therapy applications. Graphical abstract

Mucopolysaccharide polysulfate increases local skin blood volume through nitric oxide production

BackgroundMucopolysaccharide polysulfate (MPS) is widely used as an active ingredient in topical preparations for the treatment of asteatosis and blood flow disorders. Although topical MPS products can increase cutaneous blood flow (CBF), the underlying mechanism remains unclear. ObjectiveIn this study, we aimed to elucidate how MPS increases CBF. We investigated the association of nitric oxide (NO), a powerful mediator associated with increased local blood volume, with the blood flow-accelerating action of MPS in mice. In addition, we verified the effects of MPS on NO production in different skin cell types, such as keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs). MethodsWe used raster-scanning optoacoustic imaging mesoscopy to observe in vivo changes in the skin blood volume. NO production was determined in each cell using an NO indicator. An enzyme-linked immunoassay was used to measure the phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs in the presence or absence of MPS. ResultsTopical application of MPS increased the skin blood volume in mice, and this increase was abolished through the addition of NOS inhibitors. MPS promoted the dose-dependent production of NO in various cells, which caused alterations in the phosphorylation state of NOS. ConclusionOur findings demonstrate that MPS promotes an increase in skin blood volume and NO production in various skin cell types. These results suggest that MPS can potentially accelerate CBF through the NO biosynthesis pathway in different skin cell types.

Lipidomics of Microplasma-Irradiated Cells at Optimized Discharge Conditions for the Absorption of High-Molecule Drug

Microplasma irradiation is a promising technique for the transdermal delivery of high-molecular-weight drugs. In this technique, microplasma components interact with the skin surface or cell membranes, allowing the drugs to penetrate. For efficient and safe drug delivery, it is crucial to understand these interactions. To this end, this study investigated the effects of microplasma irradiation on cellular lipids, particularly those associated with cell membranes. Rat intestinal epithelial cells were treated with microplasma irradiation at two different voltages (4.0 kV or 4.5 kV). An untargeted lipidomic was conducted using liquid chromatography–mass spectrometry (LC/MS) technique. The results revealed that microplasma irradiation at 4.0 kV induces a significant increase in cell membrane lipids within 10 min post-irradiation. All major cell membrane lipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin, exhibited increases of over 25% within this short timeframe. Notably, this effect is transient, as lipid levels return to their baseline after 12 h. Furthermore, no significant differences in live and apoptotic cell percentages were observed between the control and 12 h post-irradiated cells. In contrast, irradiation at 4.5 kV did not elicit significant changes in cell membrane lipids, correlating with the absence of drug absorption under this condition. Hence, our study unveiled a correlation between the rapid increase in cell membrane lipids and enhanced drug absorption in microplasma-irradiated cells. This lipid augmentation potentially enhances membrane fluidity and permeability, thus facilitating drug absorption. Beyond elucidating the mechanisms and safety of microplasma-based drug delivery, our research provides valuable insights for advancing various microplasma-based biomedical technologies.

Characterization Methods for Nanoparticle-Skin Interactions: An Overview.

Research progresses have led to the development of different kinds of nanoplatforms to deliver drugs through different biological membranes. Particularly, nanocarriers represent a precious means to treat skin pathologies, due to their capability to solubilize lipophilic and hydrophilic drugs, to control their release, and to promote their permeation through the stratum corneum barrier. A crucial point in the development of nano-delivery systems relies on their characterization, as well as in the assessment of their interaction with tissues, in order to predict their fate under in vivo administration. The size of nanoparticles, their shape, and the type of matrix can influence their biodistribution inside the skin strata and their cellular uptake. In this respect, an overview of some characterization methods employed to investigate nanoparticles intended for topical administration is presented here, namely dynamic light scattering, zeta potential, scanning and transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared and Raman spectroscopy. In addition, the main fluorescence methods employed to detect the in vitro nanoparticles interaction with skin cell lines, such as fluorescence-activated cell sorting or confocal imaging, are described, considering different examples of applications. Finally, recent studies on the techniques employed to determine the nanoparticle presence in the skin by ex vivo and in vivo models are reported.

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.