Search Results (47)

Background/Objectives: The present study aimed to synthesize folate-conjugated poloxamers and develop polymeric micelles for the dermal delivery of irinotecan and alpha-mangostin for the treatment of melanoma using poloxamer 188 and poloxamer 184, which have never been synthesized with folate before. Methods: Poloxamer 188 and poloxamer 184 were synthesized with folate by esterification. The in vitro skin penetration enhancement of irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles was evaluated. The skin penetration pathway of folate-conjugated polymeric micelles was investigated by colocalization of multiple fluorescently labeled particles using confocal laser scanning microscopy (CLSM). Results: Folate-conjugated poloxamer 188 and poloxamer 184 were successfully synthesized. The prepared irinotecan- and alpha-mangostin-loaded folate-conjugated polymeric micelles from poloxamer 188 and poloxamer 184 had particle sizes of approximately 180 and 150 nm, respectively, indicating a positive charge with a narrow size distribution which could be easily taken up into cells. An in vitro skin penetration study revealed that folate-conjugated polymeric micelles from poloxamer 184 significantly enhanced the skin penetration of irinotecan and alpha-mangostin to a greater extent than the solution. CLSM visualization revealed that folate-conjugated polymeric micelles penetrated through the skin by the transfollicular pathway as the major penetration pathway, whereas penetration by the intercluster pathway, transcellular pathway and intercellular pathway constituted a minor pathway. Conclusions: Folate-conjugated poloxamer 184 polymeric micelles are promising candidates for the dermal delivery of anticancer drugs by the transfollicular pathway as the major skin penetration pathway. Full article

This review explores the enhanced transdermal therapy of several skin disorders with the application of carriers comprising phospholipid vesicular gel systems. Topical drug delivery has several advantages compared to other administration methods, including enhanced patient compliance, the avoidance of the first-pass impact associated with oral administration, and the elimination of the need for repeated doses. Nonetheless, the skin barrier obstructs the penetration of drugs, hence affecting its therapeutic efficacy. Carriers with phospholipid soft vesicles comprise a novel strategy used to augment drug delivery into the skin and boost therapeutic efficacy. These vesicles encompass chemicals that possess the ability to fluidize phospholipid bilayers, producing a pliable vesicle that facilitates penetration into the deeper layers of the skin. Phospholipid-based vesicular carriers have been extensively studied for improved drug delivery through dermal and transdermal pathways. Traditional liposomes are limited to the stratum corneum of the skin and do not penetrate the deeper layers. Ethosomes, glycerosomes, and glycethosomes are nanovesicular systems composed of ethanol, glycerol, or a combination of ethanol and glycerol, respectively. Their composition produce pliable vesicles by fluidizing the phospholipid bilayers, facilitating deeper penetration into the skin. This article examines the impact of ethanol and glycerol on phospholipid vesicles, and outlines their respective manufacturing techniques. Thus far, these discrepancies have not been analyzed comparatively. The review details several active compounds integrated into these nanovesicular gel systems and examined through in vitro, in vivo, or clinical human trials involving compositions with various active molecules for the treatment of various dermatological conditions. Full article

The harmful effects of solar radiation on the skin are known and scientifically proven, with recent studies indicating that not only ultraviolet (UV) radiation but also infrared (IR) radiation contributes to skin photoaging and increases the risk of carcinogenesis. Infrared radiation is also responsible for the degradation of protective carotenoids in the skin, the disruption of calcium homeostasis, and the activation of apoptosis pathways. The biological mechanisms underlying these effects include an increased level of reactive oxygen species and increased expression of metalloproteinases in the skin. The aim of this study was to evaluate the photoprotective properties of 10 cold-pressed plant oils in the infrared spectral range from 1000 nm to 2500 nm by assessing their impact on the directional–hemispherical reflectance (DHR) of human skin after their topical application. This study was conducted in vivo on the skin of 12 volunteers, with non-invasive DHR measurements taken before and directly after the application of the oil and 30 min later. Additionally, the correlation between the oil’s compounds (chlorophyll a, chlorophyll b, lycopene, and β-carotene) and antioxidant activity, expressed as the DPPH free radical scavenging capacity, was analyzed in relation to the differences in the skin’s DHR observed. An interesting result was obtained in the context of protecting the skin against IR radiation. A statistically significant increase in the skin’s reflectance after the penetration of the oil (p < 0.05) was observed in the 1700–2500 nm range for the chokeberry, fig, pomegranate, and perilla oils, suggesting their potential as photoprotective agents against IR. These findings indicate that chokeberry, fig, pomegranate, and perilla oils may serve as ingredients in cosmetic formulations designed for broad-spectrum skin photoprotection, complementing traditional UV filters with additional protection against infrared radiation. However, further research is needed to confirm these findings in a larger population. Full article

Exposure to ultraviolet (UV) radiation is a primary risk factor for various skin disorders, including erythema, sunburn, and skin cancer. Sunscreens containing UV filters, categorized as organic or inorganic, are widely utilized to mitigate these effects. Among inorganic UV filters, titanium dioxide (TiO₂) and zinc oxide (ZnO) are prominently used due to their favorable safety and achievable broad-spectrum protection profiles. This review focuses on the properties, safety, and efficacy of TiO₂ and ZnO in sunscreens, emphasizing their mechanisms of action, photostability, and impacts on human health and the environment. Key factors influencing their performance include particle size, surface coatings, and formulation pH. Despite recognized advantages, concerns about toxicity—particularly related to nanoparticle penetration and reactive oxygen species generation—highlight the need for robust safety assessments. Additionally, the environmental impacts of inorganic UV filters, including bioaccumulation and effects on aquatic ecosystems, warrant consideration. Advances in nanoparticle synthesis, bioactive compound integration, and environmentally friendly formulations offer pathways to enhance sunscreen efficacy and safety, providing opportunities for innovation in photoprotection. Full article

Psoriasis is a chronic and recurrent inflammatory disease driven not only by intrinsic factors such as immune system dysregulation but also by external factors, including bacterial infections. In contrast to the control of a single pathogenic pathway, combination therapies addressing both the immune and infectious components of psoriasis pathogenesis may offer a more effective strategy for controlling its progression. In this study, we developed a sprayable hydrogel incorporating tea polyphenol-loaded lauric acid liposomes (TP@LA-Lipo gel) to investigate its anti-inflammatory and antibacterial role in psoriasis. Our results demonstrated that TP@LA-Lipo modulated macrophage activity, reduced the expression of iNOS and TNF-α, and remodeled the immune microenvironment. Meanwhile, TP@LA-Lipo effectively eliminated Staphylococcus aureus and Escherichia coli through membrane disruption, mitigating the provoked inflammatory response. More importantly, TP@LA-Lipo gel, when sprayed onto the psoriasis lesions, provided sustained drug release over three days, enabling deeper penetration through the thickened stratum corneum to reach the inflamed layers beneath. Furthermore, in an imiquimod-induced psoriasis mouse model, TP@LA-Lipo gel effectively restored the damaged skin, alleviated histopathological changes, and reduced the systemic immune response. In summary, these findings indicate that TP@LA-Lipo gel offers a comprehensive strategy for effective disease management and improving the quality of life for psoriasis patients. Full article

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings. Full article

The depletion of the ozone layer has intensified ultraviolet (UV) radiation exposure, leading to oxidative stress, DNA damage, inflammation, photoaging, and skin cancer. Medicinal plants, widely used in Traditional Herbal Medicine (THM), particularly in Traditional Chinese Medicine (TCM), have demonstrated significant therapeutic potential due to their well-characterized active compounds and established photoprotective effects. This review systematically evaluates 18 medicinal plants selected based on their traditional use in skin-related conditions and emerging evidence supporting their efficacy against UV-induced skin damage. Their bioactive components exert antioxidant, anti-inflammatory, DNA repair, and depigmentation effects by modulating key signaling pathways, including Nrf2/ARE-, MAPK/AP-1-, PI3K/Akt-, and MITF/TYR-related melanogenesis pathways. Moreover, novel drug delivery systems, such as exosomes, hydrogels, and nanoemulsions, have significantly enhanced the stability, bioavailability, and skin penetration of these compounds. However, challenges remain in standardizing plant-derived formulations, elucidating complex synergistic mechanisms, and translating preclinical findings into clinical applications. Future interdisciplinary research and technological advancements will be essential to harness the full therapeutic potential of medicinal plants for UV-induced skin damage prevention and treatment. Full article

Caffeine has recently attracted attention as a potential remedy for hair loss. In the present review, we look into the molecule’s possible mechanisms of action and pharmacodynamics. At the molecular level, it appears that the physiological effects of caffeine are mainly due to the molecule’s interaction with adenosine pathways which leads to an increase in cAMP level and the stimulation of metabolic activity in the hair follicle. Moreover, caffeine also acts as an antioxidant and may prevent degenerative processes. While the intact stratum corneum seems virtually impenetrable to caffeine and a range of physical and chemical methods have been proposed to facilitate its penetration, hair follicles seem to be both a main entry route into the skin and target structures for caffeine at the same time. Caffeine readily forms bonds with water and other molecules which may influence its bioavailability and should be taken into account when engineering future hair products. The results of clinical studies published so far seem promising; however, the majority of the studies of caffeine-based hair loss products offer a very low level of evidence due to considerable flaws in study designs. Nevertheless, the metabolic activity of caffeine and its ability to enter and accumulate in the hair follicles combined with the results of available clinical trials seem to indicate that caffeine could indeed prove as an effective and safe option in the management of hair loss. Full article

(1) Background: Ultraviolet radiation takes part in photoaging and pigmentation disorders on skin. Epigallocatechin gallate (EGCG) is a well-known brightening and photoprotective compound but it faces limitations in terms of stability and solubility. (2) Methods: A more stable and water-soluble glucoside called EGCG-G1 was obtained by enzymatic glucosylation of EGCG. In vitro and ex vivo experiments evaluated EGCG-G1 skin penetration, antioxidant activity, and antimelanogenic properties compared to EGCG. This gene expression study characterized the pathways impacted by EGCG-G1. Four clinical studies covering phototypes I to V, at various ages, and different skin areas, using several tools, were conducted to assess the effect of EGCG-G1 on skin hyperpigmentation and tone. The impact of glucoside on skin microbiota, especially Lactobacillus sp., was assessed through in vitro and in vivo investigations. (3) Results: EGCG-G1 better penetrated the epidermis than EGCG due to a possible interaction with GLUT1. EGCG-G1 presented similar antioxidant activity to that of EGCG and decreased melanogenesis through the inhibition of 13 genes, including MITF. The skin Lactobacillus population increased with EGCG-G1, which promoted bacterial growth in vitro as prebiotic, and induced the release of a microbial brightening metabolite. Clinical trials demonstrated EGCG-G1 to decrease hyperpigmented spots and increase skin brightness and homogeneity in a large panel of phototypes, outperforming EGCG and vitamin C. (4) Conclusions: Glucosylation of EGCG maintained its photoprotective antioxidant properties and enhanced penetration across the epidermis. EGCG-G1 demonstrated brightening properties on all skin types by down-regulation of melanogenesis pathways and indirectly by skin microbiota stimulation. Full article

This literature review investigated the anti-inflammatory properties of brown algae, emphasizing their potential for dermatological applications. Due to the limitations and side effects associated with corticosteroids and immunomodulators, interest has been growing in harnessing therapeutic qualities from natural products as alternatives to traditional treatments for skin inflammation. This review explored the bioactive compounds in brown algae, specifically looking into two bioactive compounds, namely, fucoidans and phlorotannins, which are widely known to exhibit anti-inflammatory properties. This review synthesized the findings from various studies, highlighting how these compounds can mitigate inflammation by mechanisms such as reducing oxidative stress, inhibiting protein denaturation, modulating immune responses, and targeting inflammatory pathways, particularly in conditions like atopic dermatitis. The findings revealed species-specific variations influenced by the molecular weight and sulphate content. Challenges related to skin permeability were addressed, highlighting the potential of nanoformulations and penetration enhancers to improve delivery. While the in vivo results using animal models provided positive results, further clinical trials are necessary to confirm these outcomes in humans. This review concludes that brown algae hold substantial promise for developing new dermatological treatments and encourages further research to optimize extraction methods, understand the molecular mechanisms, and address practical challenges such as sustainability and regulatory compliance. This review contributes to the growing body of evidence supporting the integration of marine-derived compounds into therapeutic applications for inflammatory skin diseases. Full article

Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals which affects human health by penetrating both the respiratory system and skin, causing oxidative stress and inflammation. This review investigates the association between PM and skin disease, focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis, psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA, impairing cellular functions and triggering inflammatory responses through pathways like aryl hydrocarbon receptor (AhR), NF-κB, and MAPK. This leads to increased production of inflammatory cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion, PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation through mechanisms like ROS generation and activation of key pathways, leading to cellular damage, apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments to mitigate PM-induced skin damage. Full article

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies. Full article

Melanocytes, located in the epidermis’ basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions. Full article

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action—eosinophilic cationic proteins’ effects and allergens’ proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen–immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients. Full article

Given the broad and intense use of plastic, society is being increasingly affected by its degradation and by-products, particularly by microplastics (MPs), fragments smaller than 5 mm in size, and nanoplastics (NPs), with sizes less than 1 µm. MPs and NPs may enter the body primarily through inhalation, consumption, and skin contact. Once ingested, MPs can penetrate tissues, deviating to other parts of the body and potentially affecting important cellular pathways such as nonconforming chemokine receptors that control the communication between the fetus and the mother. Consequently, the potential health harm induced via MP internalization is a major issue, evidenced by multiple studies demonstrating harmful consequences in diverse animal models and human cells. Here, an overview of the various modes of exposure to MPs and NPs is presented, including inhalation, placental transfer, ingestion, breastmilk consumption, and skin absorption, as well as placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Though MPs in our environment are becoming more recognized, their developmental toxicity is still scarcely known. Besides negatively affecting pregnancy, MPs and NPs have been shown to potentially harm the developing fetus, given their ability to cross the placental barrier. Still, considerable gaps remain in our understanding of the dispersion and toxicity of these particles in the environment and the precise types of NPs and MPs bearing the greatest dangers. As a result, we advocate for larger-scale epidemiological investigations, the development of novel approaches for measuring NP and MP exposures, and the necessity of understanding the toxicity of various kinds of NPs to guide future research efforts. Full article