Search Results (2,809)

Background: Methotrexate (MTX) is a well-established therapeutic agent for psoriasis owing to its anti-inflammatory and immunomodulatory effects. However, its clinical use is limited by insufficient local accumulation in skin lesions and the potential risk of systemic exposure. Dunaliella salina-derived exosome (DsEXO) has favorable biocompatibility, low immunogenicity and potential skin delivery capacity, making it a promising natural nanocarrier for topical MTX delivery. This study aimed to construct Dunaliella salina-derived exosome loaded with methotrexate (DsEXO@MTX) and evaluate its therapeutic efficacy and potential mechanisms in psoriasis-like skin inflammation. Methods: DsEXO@MTX was prepared and characterized in terms of morphology, particle size, surface charge and drug-loading capacity. Cellular uptake, skin retention and tissue distribution were evaluated using fluorescence imaging and skin section analysis. Therapeutic efficacy was evaluated in an imiquimod-induced psoriasis-like mouse model by clinical scoring, histopathological examination, spleen index measurement and Ki-67 immunofluorescence staining. STAT3 phosphorylation and Th17/Treg differentiation were further examined to explore the potential immunomodulatory mechanism. Results: DsEXO@MTX exhibited a relatively uniform particle size distribution and drug-loading capacity. In vivo fluorescence imaging and skin section analysis showed that DsEXO@MTX enhanced local skin retention and promoted fluorescence distribution in epidermal and dermal regions. It significantly alleviated IMQ-induced erythema, scaling, epidermal thickening, inflammatory infiltration, splenomegaly and abnormal keratinocyte proliferation in psoriasis-like mice. Mechanistically, DsEXO@MTX reduced STAT3 phosphorylation and modulated Th17/Treg differentiation, suggesting restoration of immune balance in psoriatic inflammation. Conclusions: DsEXO@MTX represents a natural exosome-like nanovesicle-mediated topical MTX delivery system that improves local drug delivery and enhances therapeutic efficacy in IMQ-induced psoriasis-like skin inflammation, particularly when administered topically. These findings provide a potential strategy for safer and more efficient local treatment of psoriasis. Full article

Background/Objectives: Androgenetic alopecia (AGA) is the most prevalent form of hair loss. Although topical minoxidil (MNX) is widely used to treat AGA, its efficacy is limited by poor penetration across the stratum corneum. This study evaluated radiofrequency (RF) microporation as a means of enhancing cutaneous MNX delivery and hair-regrowth efficacy in a dihydrotestosterone (DHT)-induced AGA mouse model. Methods: RF-induced skin permeabilization and barrier recovery were assessed in rats using methylene blue and rhodamine B staining. In vivo skin deposition and pharmacokinetic studies were conducted to quantify cutaneous MNX accumulation and systemic exposure. Hair-regrowth efficacy was evaluated in DHT-treated mice. Results: RF microporation generated transient microchannels in the stratum corneum, increased rhodamine B penetration into deeper skin layers, and allowed substantial barrier recovery within 24 h. RF pretreatment significantly increased MNX deposition in the epidermis/dermis by 2.40-fold at 1 h and 1.94-fold at 3 h compared with topical MNX alone. RF-assisted topical administration resulted in a relative bioavailability of 11.17%, compared with 4.74% for topical administration without RF, while dose-normalized systemic exposure remained substantially lower than that following oral administration. In the AGA model, RF-assisted MNX treatment significantly increased hair coverage, length, and shaft thickness. Histological analysis further showed more prominent follicular structures in the RF-assisted MNX groups. Conclusions: RF microporation creates transient microchannels that enhance cutaneous MNX delivery and improve hair-regrowth efficacy. Importantly, RF-assisted topical administration maintained substantially lower systemic exposure than oral administration, supporting its potential as a needle-free strategy for topical AGA therapy and further translational evaluation. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, microbial imbalance, and severe pruritus. Emerging evidence establishes that barrier disruption is a central pathogenic driver capable of initiating inflammatory signaling, neuroimmune activation, and chronic disease instability. This understanding has shifted therapeutic paradigms toward barrier-directed strategies aimed at restoring epidermal resilience. This narrative review evaluates the mechanistic and clinical evidence surrounding isosorbide fatty acid diester molecules—specifically isosorbide dicaprylate (IDC) and isosorbide di-(linoleate/oleate) (IDL)—as a barrier-first approach for AD management. Early in vitro and ex vivo investigations demonstrated that IDC significantly improves epidermal hydration, transepidermal water loss, and the expression of barrier-associated genes linked to epidermal integrity. Subsequent studies showed that IDL expands these effects through coordinated regulation of keratinocyte differentiation, lipid homeostasis, and inflammatory stress pathways. Furthermore, recent mechanistic data highlight synergistic anti-inflammatory and pruritus-modulating effects involving TRPA1-, TRPV3-, and TSLP-associated pathways, while preserving tissue integrity under cytokine-induced stress. Clinically, these findings are supported by randomized studies in pediatric and adult cohorts demonstrating significant reductions in pruritus, favorable Eczema Area and Severity Index (EASI) responses, decreased topical corticosteroid dependence, and a reduction in the relative abundance of Staphylococcus aureus. Collectively, these findings support a barrier-first therapeutic framework in which restoration of epidermal resilience may beneficially influence multiple interconnected pathways involved in atopic dermatitis. Full article

Agarose is a thermoreversible, highly biocompatible polysaccharide increasingly used in tissue engineering (TE). Its molecular architecture, optical clarity, tunable mechanics, and chemical inertness make agarose hydrogels attractive scaffolds for generating bioartificial tissues by TE. This review summarizes current knowledge on agarose extraction, purification, structural variants, and physicochemical properties regarding gelation behavior, stiffness, porosity, and bioactivity. We discuss how agarose type and concentration critically determine hydrogel biomechanical and optical performance, influencing cell behavior and in vivo suitability. Although biologically inert, agarose can be functionalized or combined with fibrin, collagen, chitosan, and other biomaterials to enhance cell adhesion, proliferation, and differentiation. Diverse biofabrication approaches—including micromolding, bead production, 3D bioprinting, and de novo assembly of cells, biomaterials and bioactive factors—have enabled the generation of microtissues, organoids, and complex multilayered constructs. Agarose-based biomaterials allowed for the successful generation of bioartificial substitutes of cartilage, bone, adipose tissue, skin, cornea, oral mucosa, and the peripheral nerve, with several fibrin-agarose advanced therapy medicinal products (ATMP) already reaching clinical application, including the skin substitute UGRSKIN, the artificial cornea NANOULCOR and the palate mucosa BIOCLEFT. Together, current evidence positions agarose as a versatile and translationally relevant biomaterial for next-generation TE, warranting further exploration of its potential in additional therapeutic contexts. Full article

Hyaluronic acid (HA) is a high-molecular-weight glycosaminoglycan whose cross-linked hydrogels are widely used as injectable fillers; their controlled degradation is clinically important but, in practice, achievable only enzymatically with hyaluronidase. Here we compared the enzymatic, ultrasonic and photothermal degradation of a single cross-linked HA macromolecular network and characterised the resulting structural, thermal and chromatographic changes. A cross-linked HA hydrogel (Regenyal Idea, 25 mg/mL) was embedded in an ex vivo porcine skin matrix and treated in six groups: untreated control; hyaluronidase; microfocused ultrasound (7 MHz, 3 mm focal depth); and irradiation with 1064 nm Nd:YAG, diode or alexandrite lasers. Degradation was characterised by FT-IR spectroscopy, thermogravimetric analysis (TGA) and high-performance liquid chromatography (HPLC). FT-IR showed retention of the HA backbone with partial loss of the cross-linked network, while TGA revealed treatment-dependent decreases in thermal stability. By HPLC, hyaluronidase released the most soluble HA (58.2 ± 2.9% at day 1; ~88% plateau by day 2). Among the energy-based methods, only the 1064 nm Nd:YAG laser produced comparable degradation (57.3 ± 5.2%), whereas microfocused ultrasound, the diode and the alexandrite lasers released little soluble HA (3.2–5.3%). The wavelength dependence is consistent with a water-mediated photothermal scission of the HA chains. These findings identify long-pulsed 1064 nm irradiation as an effective non-enzymatic route to degrade the cross-linked hyaluronic acid macromolecule, with hyaluronidase remaining the reference standard. Full article

Visible light (VL) accounts for approximately 50% of the solar radiation reaching Earth’s surface and has emerged as a major contributor to skin photoaging and pigmentation disorders, particularly in individuals with darker Fitzpatrick skin phototypes. Increasing evidence suggests that VL exposure induces oxidative stress, inflammation, and melanogenesis by generating reactive oxygen species. In this study, we investigated the protective effects of a topical antioxidant formulation (AOX Mix) containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol against VL exposure in ex vivo skin biopsies from donors with Fitzpatrick skin phototypes IV–V. To preserve physiological tissue tension and closely replicate in vivo skin responses, human skin explants were maintained using the TenSkin™ culture system. Samples were pretreated with AOX Mix for 30 min, then exposed to VL for 8 h, and collected on Days 2 and 7 for histological and molecular analyses. Our results demonstrated that prolonged exposure to VL disrupted redox homeostasis and induced structural alterations in skin explants, accompanied by increased markers of oxidative stress and pigmentation. In contrast, pre-treatment with AOX Mix significantly attenuated these effects, preserving tissue architecture and reducing molecular indicators of photodamage. In addition, we observed the co-localization of 4-hydroxynonenal and collagen type I, suggesting that oxidative post-translational modification of collagen may contribute to its loss. These findings suggest that antioxidant-based interventions, such as AOX Mix, may be a promising strategy for protecting dark skin against VL exposure. Full article

Dissolving microneedles offers a minimally invasive approach for transdermal drug delivery by facilitating drug transport across the stratum corneum while overcoming several limitations associated with conventional routes of administration. Benzhydroxamic acid has demonstrated biochemical and computational evidence associated with inflammatory and pain-related pathways; however, its incorporation into a dissolving microneedle platform has not been extensively explored.This study aimed to fabricate and characterize benzhydroxamic acid-loaded dissolving microneedles using a 3D-printing-assisted mold fabrication approach for transdermal drug delivery. A stereolithography-based 3D-printed master mold was used to prepare a reverse polydimethylsiloxane mold. Benzhydroxamic acid-loaded dissolving microneedles were fabricated using a PVA/PVP polymeric matrix and evaluated for their physicochemical, mechanical, insertional, and drug-delivery characteristics. The developed microneedles exhibited shear-thinning behavior, uniform morphology, and satisfactory mechanical properties, with a compression force of 3.5 ± 0.01 N/needle and tensile strength of 3.84 ± 0.21 MPa. The formulation demonstrated a drug-loading efficiency of 94.6 ± 0.35% and effective insertion into the Parafilm^® M skin-simulant model. In vitro drug release reached 97.24% over 24 h, while ex vivo skin permeation reached 94.83% over 24 h. FTIR and XRD analyses indicated successful incorporation of benzhydroxamic acid into the PVA/PVP matrix without major evidence of drug–polymer incompatibility. The findings demonstrate the feasibility of incorporating benzhydroxamic acid into a PVA/PVP dissolving microneedle platform using a 3D-printing-assisted mold fabrication approach. The developed system exhibited suitable physicochemical and mechanical characteristics, efficient drug loading, effective insertion, and satisfactory in vitro and ex vivo drug-delivery performance, supporting its potential as a transdermal drug delivery platform. Full article

Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) is a medicinal plant, renowned since antiquity, widely used in traditional medicine for the management of metabolic and inflammatory disorders: seed extracts particularly are reported for the management of rheumatoid arthritis, articular inflammation and skin wound recovery. Our aim was to comparatively evaluate the antioxidant and anti-inflammatory activities of aqueous and oily extracts obtained from mature and immature seeds, and to preliminarily assess their dermal tolerance and protective effects against induced inflammation and UV damage. Antioxidant activity was investigated in vitro using β-carotene bleaching and ferric reducing antioxidant power (FRAP) assays, whereas anti-inflammatory activity and anti-irritation effects were evaluated in vivo in a mouse model using the xylene-induced ear edema and the UV-induced skin irritation test. Oily extracts from both maturation stages showed marked inhibition of β-carotene oxidation, while the aqueous extract of immature seeds exhibited the highest ferric reducing capacity; on the other hand, fixed oils demonstrated a significantly greater inhibitory effect on oedema, suggesting a higher efficacy in modulating acute inflammatory responses. Results showed how C. colocynthis seed maturity and extraction solvent influence the bioactive potential of these ingredients for phytotherapeutic and dermo-functional applications, supporting a possible use against wrinkle formation and UV-induced skin alterations. Full article

Skin photoaging resulting from chronic ultraviolet A (UVA) exposure is closely associated with mitochondrial dysfunction and impaired cellular homeostasis. Mitophagy is an important mitochondrial quality control process, but the role of FUNDC1-associated mitophagy-related activity in skin photoaging remains incompletely understood. Here, we investigated the function and regulatory mechanisms of FUNDC1 in UVA-induced photoaging models. FUNDC1 expression was reduced in UVA-exposed human dermal fibroblasts (HDFs) and in photoaged mouse skin. FUNDC1 knockdown aggravated photoaging-associated phenotypes, mitochondrial dysfunction, and altered autophagy/mitophagy-related activity, whereas FUNDC1 overexpression attenuated these changes in vitro and in vivo. Pharmacological modulation further showed that Rapa partially counteracted FUNDC1 knockdown-associated effects, while Mdivi-1 weakened the protective effects associated with FUNDC1 overexpression, supporting the involvement of mitophagy-related mitochondrial quality control. Mechanistically, miR-137-3p was upregulated during UVA-induced photoaging and negatively regulated FUNDC1 expression through the predicted FUNDC1 3′UTR binding site. In addition, FUNDC1 was concerned with proteasome-dependent regulation of P53 protein stability. BAZ1B was identified as a candidate P53-associated ubiquitination regulator that participated in FUNDC1-associated regulation of P53 ubiquitination and stability. LC-MS/MS analysis combined with site-directed mutagenesis further manifested that P53 K292 was a major ubiquitination site involved in BAZ1B-associated regulation of P53 stability. In vivo, BAZ1B knockdown attenuated FUNDC1-associated protection against UVA-induced skin photoaging and reduced P53 ubiquitination. Collectively, these findings indicate that FUNDC1 can attenuate UVA-induced skin photoaging by preserving mitophagy-related mitochondrial homeostasis and modulating BAZ1B-associated P53 stability, with miR-137-3p acting as an upstream negative regulator of FUNDC1. Full article

Antimicrobial resistance has intensified the search for novel antimicrobial and wound-healing agents. Ludwigia octovalvis (Jacq.) P.H. Raven is traditionally used to treat infections, inflammation, and skin disorders, although its in vitro biotechnological potential remains largely unexplored. This study reports the first successful establishment of L. octovalvis callus cultures, their characterization by gas chromatography-mass spectrometry (GC-MS), and the evaluation of their antimicrobial and wound-healing activities. Friable calluses were induced from leaf and node explants of axenic seedlings using combinations of 6-benzylaminopurine (BAP), kinetin (KIN), 2,4-dichlorophenoxyacetic acid (2,4-D), and α-naphthaleneacetic acid (NAA). Optimal callus induction was achieved in leaf explants cultured on full-strength Murashige and Skoog (MS) medium supplemented with BAP (4.44 µM) and 2,4-D (0.45 µM). After six months of subculture, the calluses showed morphological uniformity and stable biomass production. Growth kinetics followed a specific growth rate of 0.047 d⁻¹ and a doubling time of 14.54 days. GC-MS analysis identified fatty acids and phytosterols as the main components. The ethyl acetate extract significantly improved wound healing in vivo, while the methanolic extract exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). These findings demonstrate that L. octovalvis callus cultures constitute a sustainable source of bioactive compounds with promising therapeutic potential. Full article

Background: Plants have been traditionally used for centuries to treat wounds and, over time, have been tested for their healing properties. There is a constant search for new natural resources that could be used to develop various topical wound care products. Methods: A comprehensive search of the literature was conducted in PubMed/MEDLINE, Scopus, and Web of Science databases (2022–2026) in accordance with the PRISMA 2020 guidelines. Included studies focused on current in vitro and in vivo research on hydrogels containing plant extracts from the Asteraceae and Lamiaceae families and their potential application in wound healing and skin regeneration. Results: An analysis of 24 included studies confirms that both families include interesting and valuable plants with antioxidant, antimicrobial and anti-inflammatory properties; these plants also influence collagen deposition, fibroblast proliferation, and epithelialization, and reduce the risk of infection, thereby contributing to faster wound healing. The most frequently tested phytoextract in this respect was Calendula officinalis (Asteraceae) incorporated into a hydrogel. A variety of materials, including natural, semi-synthetic, and synthetic polymers, as well as hybrid matrix, but also diverse formulation strategies, from simple solutions to more advanced and modern methods, have been used to produce hydrogels. Conclusions: This systematic review summarizes the current evidence, highlights directions and possibilities for the use of phytoextract-based hydrogels, and discusses limitations and future perspectives in the development of effective externally applied formulations to support wound healing. Full article

Skin photoaging is closely associated with oxidative stress, inflammatory responses, and dysregulated collagen metabolism. Paeonol (Pae) possesses antioxidant and anti-inflammatory activities; however, its poor water solubility and short skin retention time limit its topical application. In this study, a transdermal delivery system based on a carboxymethyl chitosan (CMCS)/Carbomer 940 (Carb940) composite gel loaded with hydroxypropyl-β-cyclodextrin inclusion complexes of paeonol (Pae-CD) was developed. Pae-CD was prepared using an ultrasound-assisted saturated aqueous solution method, and the physicochemical properties, sustained-release behavior, transdermal permeation, antioxidant activity, and safety of Pae-CD/gel were evaluated. Furthermore, a mouse model of skin photoaging induced by combined ultraviolet A (UVA)/ultraviolet B (UVB) irradiation was established to investigate its reparative effects in vivo. The results showed that Pae-CD/gel exhibited a homogeneous three-dimensional porous structure, favorable sustained-release characteristics, enhanced skin retention capacity, and good cellular compatibility. In vivo experiments demonstrated that Pae-CD/gel markedly ameliorated ultraviolet-induced skin dryness, abnormal epidermal thickening, and dermal collagen loss. It also reduced oxidative stress and inflammatory factor levels, down-regulated matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) expression, and promoted the restoration of collagen type I (COL-1) and hydroxyproline (HYP) levels. Systemic safety evaluation revealed no obvious toxicity. In summary, Pae-CD/gel exerts antioxidant and anti-inflammatory effects and regulates collagen metabolism by enhancing transdermal delivery and local retention, thereby providing a safe and effective topical delivery strategy for the repair of skin photoaging. Full article

Optical imaging technologies are increasingly reshaping the interface between clinical dermatology and dermatopathology. In vivo reflectance confocal microscopy (IV-RCM), line-field confocal optical coherence tomography (LC-OCT), and ex vivo confocal microscopy (EV-CM) provide tissue-level morphological information without the need for conventional histopathologic processing or with substantially reduced processing times. These technologies have enabled the concept of the “virtual biopsy” and are increasingly integrated into diagnostic workflows. However, their clinical value cannot be understood solely through conventional diagnostic performance metrics such as sensitivity and specificity. Rather, their impact depends on how the information they generate is incorporated into sequential diagnostic pathways and clinical decision-making processes. This review summarizes the principles, current applications, diagnostic performance, limitations, and future prospects of IV-RCM, LC-OCT, and EV-CM. We discuss the complementary strengths of these modalities and propose a systems perspective in which imaging technologies are viewed as components of diagnostic ecosystems linking clinical examination, dermatoscopy, pathology, surgery, and computational decision support. Emerging developments in artificial intelligence, multimodal imaging, and digital pathology are likely to further strengthen these connections and expand the role of optical imaging in dermatology and dermatopathology. Full article

The increasing prevalence of dermatophytosis and biofilm-associated infections highlights the need for new therapeutic approaches. This study evaluated the potential of Lavandula stoechas subsp. luisieri essential oil against clinically relevant dermatophytes. The essential oil obtained by hydrodistillation was chemically characterized by gas chromatography–mass spectrometry (GC–MS). Antifungal activity was assessed through determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), while antibiofilm activity against Epidermophyton floccosum was evaluated by measuring biofilm biomass, extracellular matrix (ECM) deposition, and cell viability. An ex vivo model of Trichophyton rubrum-induced skin infection was used to assess efficacy under tissue-relevant conditions. The essential oil was mainly composed of oxygenated monoterpenes, with trans-α-necrodyl acetate (19.1%), lavandulyl acetate (13.6%), camphor (8.8%), 1,8-cineole (6.1%), and trans-α-necrodol (5.3%) as major constituents. The oil exhibited antifungal activity against all tested dermatophytes (MIC: 12.5–100 μg/mL), induced hyphal morphological alterations, significantly inhibited E. floccosum biofilm formation, particularly ECM deposition, and reduced fungal dissemination in the ex vivo skin model. These findings support the antidermatophytic and antibiofilm potential of L. stoechas subsp. luisieri essential oil, although further studies are required. Full article

Background: The skin barrier plays a fundamental role in preventing transepidermal water loss (TEWL), regulating immune responses, and protecting against pathogen colonization. Disruption of this barrier underlies xerosis, sensitive skin, and clinical cracking. Heat-treated probiotics (postbiotics) represent a stable and biologically active approach to topical formulation. Objective: To evaluate the safety, molecular mechanisms, and clinical efficacy of heat-treated Lactiplantibacillus plantarum Skinbac™ SB14 (SB14) in improving skin barrier function, hydration, and the appearance of dry and cracked skin. Methods: In vitro studies assessed cell viability (MTT assay) and cytotoxicity (LDH release assay), Aquaporin-3 (AQP3) expression, Claudin-1 expression recovery following UV-induced damage (post-damage treatment model), cytokine modulation in Normal Human Epidermal Keratinocytes (NHEK) and Peripheral Blood Mononuclear Cells (PBMCs), and antipathogen activity against Staphylococcus aureus biofilm. A 30-day open-label, placebo-controlled clinical study (n = 20 healthy volunteers, both sexes, age > 18 years) evaluated an emulsion containing 1% SB14 versus placebo using instrumental measurements of superficial hydration (Corneometer^® CM825) and TEWL (Tewameter^® TM300), and clinical scoring of skin hydration (Kligman scale 1–4) and skin cracking (ODS Overall Dry Skin Score 1–5) via C-Cube imaging. Results: In vitro testing confirmed the safety of SB14 (full cell viability by MTT assay; no cytotoxicity by LDH release assay) and demonstrated significant AQP3 upregulation (p < 0.05), partial Claudin-1 recovery in UV-damaged cells following post-damage SB14 application (p < 0.1 vs. UV damage), significant reduction in pro-inflammatory IL-8 and IL-23 in NHEK (p < 0.01 and p < 0.05), strong innate immune activation in PBMCs (TNF-α and IL-6, p < 0.001), and 21% inhibition of S. aureus biofilm at 72 h. Clinically, the SB14 formulation significantly increased superficial skin hydration by +46.1% at T14 (p = 0.0451) and +33.6% at T30 (p = 0.0144) versus baseline, while TEWL decreased by −14.5% at T14 (p = 0.0205). Clinical hydration scores improved significantly from a median of 3.0 (moderate dry skin) at baseline to 2.0 (slightly dry skin) at T30 (p = 0.0073). Cracking scores improved significantly from a median of 3.5 at baseline to 2.0 at T30 (p = 0.0037), with 80% of subjects showing improvement at T30. All parameters remained non-significant in the placebo group. No adverse events were reported. Conclusions: SB14 is safe, biologically active across multiple barrier-relevant mechanisms, and clinically effective in improving hydration and reducing visible skin cracking in subjects with dry, barrier-compromised skin. Full article