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Search Results (514)

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Keywords = topical skin delivery

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35 pages, 1395 KiB  
Review
Local Chemotherapy of Skin Pre-Neoplastic Lesions and Malignancies from the Perspective of Current Pharmaceutics
by Nadezhda Ivanova
Pharmaceutics 2025, 17(8), 1009; https://doi.org/10.3390/pharmaceutics17081009 - 1 Aug 2025
Viewed by 396
Abstract
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while [...] Read more.
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article
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21 pages, 3048 KiB  
Article
Transfersome-Based Delivery of Optimized Black Tea Extract for the Prevention of UVB-Induced Skin Damage
by Nadia Benedetto, Maria Ponticelli, Ludovica Lela, Emanuele Rosa, Flavia Carriero, Immacolata Faraone, Carla Caddeo, Luigi Milella and Antonio Vassallo
Pharmaceutics 2025, 17(8), 952; https://doi.org/10.3390/pharmaceutics17080952 - 23 Jul 2025
Viewed by 313
Abstract
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize [...] Read more.
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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22 pages, 2224 KiB  
Article
Development and Evaluation of an Anti-Inflammatory Emulsion: Skin Penetration, Physicochemical Properties, and Fibroblast Viability Assessment
by Jolita Stabrauskiene, Agnė Mazurkevičiūtė, Daiva Majiene, Rima Balanaskiene and Jurga Bernatoniene
Pharmaceutics 2025, 17(7), 933; https://doi.org/10.3390/pharmaceutics17070933 - 19 Jul 2025
Viewed by 470
Abstract
Background/Objectives. Chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis, require safe and effective topical treatments. This study aimed to develop and evaluate a novel anti-inflammatory emulsion enriched with menthol, capsaicin, amino acids (glycine, arginine, histidine), and boswellic acid. Methods. Three formulations [...] Read more.
Background/Objectives. Chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis, require safe and effective topical treatments. This study aimed to develop and evaluate a novel anti-inflammatory emulsion enriched with menthol, capsaicin, amino acids (glycine, arginine, histidine), and boswellic acid. Methods. Three formulations were prepared: a control (E1), a partial (E2), and a comprehensive formulation (E3). Physicochemical analyses included texture profiling, rheological behavior, pH stability, moisture content, and particle size distribution. Results. E3 demonstrated superior colloidal stability, optimal pH (5.75–6.25), and homogenous droplet size (<1 µm), indicating favorable dermal delivery potential. Ex vivo permeation studies revealed effective skin penetration of menthol and amino acids, with boswellic acid remaining primarily in the epidermis, suggesting localized action. Under oxidative stress conditions, E3 significantly improved fibroblast viability, indicating synergistic cytoprotective effects of combined active ingredients. While individual compounds showed limited or dose-dependent efficacy, their combination restored cell viability to near-control levels. Conclusions. These findings support the potential of this multi-component emulsion as a promising candidate for the topical management of inflammatory skin conditions. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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23 pages, 6291 KiB  
Article
Application of Standardized Rosa damascena Stem Cell-Derived Exosomes in Dermatological Wound Healing and Scar Management: A Retrospective Case-Series Study with Long-Term Outcome Assessment
by Lidia Majewska, Agnieszka Kondraciuk, Karolina Dorosz and Agnieszka Budzyńska
Pharmaceutics 2025, 17(7), 910; https://doi.org/10.3390/pharmaceutics17070910 - 14 Jul 2025
Cited by 2 | Viewed by 728
Abstract
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of [...] Read more.
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of diverse dermatological conditions, including traumatic wounds, surgical scars, and atrophic acne scars. Methods: We conducted a case series study from June 2023 to November 2024, documenting four cases with different types of skin damage treated with lyophilized RSCE products. Treatment protocols included a variety of delivery methods such as topical application, microneedling, and post-procedure care. Follow-up assessments were performed at intervals ranging from 7 days to 10 months. Results: All patients demonstrated significant improvements in scar appearance, skin elasticity, hydration, and overall tissue quality. In traumatic facial injury, RSCE therapy facilitated reduction in scar contracture and improved functional outcomes. For atrophic acne scars, comparative treatment of facial sides showed enhanced results with RSCE addition. Acute wounds exhibited accelerated healing with reduced inflammation, while chronic wounds demonstrated improved epithelialization and long-term scar quality. Conclusions: This case series provides preliminary evidence suggesting that RSCE therapy may offer significant benefits in wound healing and scar management. The observed improvements in tissue regeneration, inflammatory modulation, and long-term aesthetic outcomes warrant further investigation through controlled clinical trials. Full article
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29 pages, 1189 KiB  
Review
Decoding Skin Aging: A Review of Mechanisms, Markers, and Modern Therapies
by Jorge Naharro-Rodriguez, Stefano Bacci, Maria Luisa Hernandez-Bule, Alfonso Perez-Gonzalez and Montserrat Fernandez-Guarino
Cosmetics 2025, 12(4), 144; https://doi.org/10.3390/cosmetics12040144 - 10 Jul 2025
Viewed by 1758
Abstract
Skin aging is a multifactorial process driven by both intrinsic mechanisms—such as telomere shortening, oxidative stress, hormonal decline, and impaired autophagy—and extrinsic influences including ultraviolet radiation, pollution, smoking, and diet. Together, these factors lead to the structural and functional deterioration of the skin, [...] Read more.
Skin aging is a multifactorial process driven by both intrinsic mechanisms—such as telomere shortening, oxidative stress, hormonal decline, and impaired autophagy—and extrinsic influences including ultraviolet radiation, pollution, smoking, and diet. Together, these factors lead to the structural and functional deterioration of the skin, manifesting as wrinkles, pigmentation disorders, thinning, and reduced elasticity. This review provides an integrative overview of the biological, molecular, and clinical dimensions of skin aging, emphasizing the interplay between inflammation, extracellular matrix degradation, and senescence-associated signaling pathways. We examine histopathological hallmarks and molecular markers and discuss the influence of genetic and ethnic variations on aging phenotypes. Current therapeutic strategies are explored, ranging from topical agents (e.g., retinoids, antioxidants, niacinamide) to procedural interventions such as lasers, intense pulsed light, photodynamic therapy, microneedling, and injectable biostimulators. Special attention is given to emerging approaches such as microneedle delivery systems, with mention of exosome-based therapies. The review underscores the importance of personalized anti-aging regimens based on biological age, phototype, and lifestyle factors. As the field advances, integrating mechanistic insights with individualized treatment selection will be key to optimizing skin rejuvenation and preserving long-term dermal health. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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22 pages, 1889 KiB  
Article
Development and Characterization of Bigels for the Topical Delivery of Curcumin
by Juan Luis Peréz-Salas, Martha Rocío Moreno-Jiménez, Luis Medina-Torres, Nuria Elizabeth Rocha-Guzmán, María Josefa Bernad-Bernad, Rubén Francisco González-Laredo and José Alberto Gallegos-Infante
Sci. Pharm. 2025, 93(3), 28; https://doi.org/10.3390/scipharm93030028 - 3 Jul 2025
Viewed by 396
Abstract
The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to [...] Read more.
The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to develop bigels for the topical delivery of curcumin. Employing a rheology test, it was found that all bigels showed a solid-like behavior structure (G′ > G″) with stiffness increasing with higher organogel content. The principle of time–temperature superposition (TTS) was used to generate master curves. Microscopy revealed a morphological structure that depended on the organogel/hydrogel ratio. The bigels exhibited a pH compatible with that of human skin, and the curcumin content met the standards for uniform dosage. Thermal characterization showed the presence of three peaks in coconut oil bigels and two peaks in castor oil bigels. Bigels with a 45% castor oil organogel/55% hydrogel ratio exhibited a longer controlled release of curcumin, while bigels with coconut oil showed a faster release. The release data were fitted to mathematical models indicating non-Fickian release. The permeability of curcumin through Strat-M membranes was investigated, and greater permeation was observed with increasing organogel content. The developed bigels could be a promising option for the topical delivery of curcumin. Full article
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11 pages, 1018 KiB  
Article
The Influence of Moisturizer Co-Application Protocols on In Vitro Penetration of Betamethasone in Porcine Skin
by Daiane L. Rost, Geisa N. Barbalho, Jayanaraian F. M. Andrade, Marcilio Cunha-Filho, Guilherme M. Gelfuso and Tais Gratieri
Pharmaceutics 2025, 17(7), 874; https://doi.org/10.3390/pharmaceutics17070874 - 3 Jul 2025
Viewed by 418
Abstract
Background/Objectives: The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, [...] Read more.
Background/Objectives: The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, application sequence, and massage affect cutaneous drug delivery. Hence, this study aimed to evaluate the effects of formulation type, moisturizer composition, application sequence, and mechanical stimulation on betamethasone dipropionate (BET) cutaneous penetration. Methods: Two commercial formulations (cream and ointment) of BET were evaluated in different experimental conditions, including drug application combined with moisturizers (Cetaphil®, as an emollient; Nivea®, as an occlusive) pre- or post-application, with or without a 30 s massage. In vitro skin penetration assays were conducted for 12 h using porcine skin mounted in modified Franz diffusion cells. BET levels were extracted from the skin layers and quantified by HPLC. Results: The cutaneous BET penetration was strongly influenced by the application sequence, type of moisturizer, and mechanical stimuli. Pre-application of an occlusive or emollient moisturizer, followed by 30 s physical stimuli, significantly enhanced drug retention in the stratum corneum. For the cream, pre-application of moisturizers followed by massage notably increased BET levels in both the stratum corneum and viable skin. Conversely, post-application of moisturizers hindered BET absorption. The ointment showed limited penetration across all conditions, with no drug detected in the viable skin. Conclusions: The results showed pre-hydrating the skin, combined with a 30 s massage, was the best strategy for BET diffusion into the skin following cream administration. The formulation type and the order of application directly influence the effectiveness of drug therapy and the topical absorption of BET. Full article
(This article belongs to the Special Issue Skin Care Products for Healthy and Diseased Skin)
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13 pages, 653 KiB  
Review
Topical Percutaneous Drug Delivery for Allergic Diseases: A Novel Strategy for Site-Directed Pharmacologic Modulation
by Mitsuhiro Kamimura, Hiroaki Todo, Kenji Sugibayashi and Koichiro Asano
Pharmaceutics 2025, 17(7), 867; https://doi.org/10.3390/pharmaceutics17070867 - 2 Jul 2025
Viewed by 343
Abstract
Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous [...] Read more.
Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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14 pages, 2404 KiB  
Article
Development of a γ-Cyclodextrin-Based Cryogel Loaded with Trimethoprim for Acne Treatment: Design, Synthesis, and In Vitro Evaluation
by Elisabetta Grazia Tomarchio, Valentina Giglio, Virginia Fuochi, Salvatore Furnari, Pio Maria Furneri, Tommaso Mecca, Sandro Dattilo, Chiara Zagni and Antonio Rescifina
Int. J. Mol. Sci. 2025, 26(13), 6319; https://doi.org/10.3390/ijms26136319 - 30 Jun 2025
Viewed by 254
Abstract
Innovative functional materials integrating host–guest complexes in cryogels offer promising applications in topical drug delivery, enhancing drug solubility and stability. In this study, we designed and developed a cryogel-based patch for acne treatment by polymerizing an acrylate-functionalized γ-cyclodextrin (γ-CD) and trimethoprim (TMP) inclusion [...] Read more.
Innovative functional materials integrating host–guest complexes in cryogels offer promising applications in topical drug delivery, enhancing drug solubility and stability. In this study, we designed and developed a cryogel-based patch for acne treatment by polymerizing an acrylate-functionalized γ-cyclodextrin (γ-CD) and trimethoprim (TMP) inclusion complex with [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMA) at low temperatures. A multistep workflow was applied to synthesize the inclusion complex via mortar-assisted kneading, followed by cryogel formulation through radical cryopolymerization. The resulting hybrid system leverages the cationic nature of AETMA to promote adhesion and electrostatic interactions with the skin surface. At the same time, γ-CD serves as a drug reservoir, facilitating sustained release of the drug. The system was characterized by FT-IR, TGA, and SEM analyses. In vitro release studies demonstrated a sustained TMP release profile, best described by the Korsmeyer–Peppas diffusion model. Antibacterial assays confirmed the system’s effectiveness against Staphylococcus aureus, supporting its potential for localized and prolonged acne treatment. Moreover, cytocompatibility tests demonstrated that the formulation is biocompatible, further validating its suitability for topical application. Full article
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30 pages, 5331 KiB  
Article
Development of a Novel Drug Delivery System “Nanoemulfoam” for Topical Delivery of Terbinafine Hydrochloride as a Repurposed Therapy in Skin Cancer: Formulation, Optimization, In Vitro Characterization, Ex Vivo Transdermal Permeability, Cytotoxicity Studies, and In Silico Assessment
by Abeer A. Musallam, Reem A. Aldeeb, Riham M. Mansour, Manar Abd El-karim Kassem, Doaa Fayez Saeed, Mahmoud A. Mahdy, Rana M. Abdelnaby, Hanan M. Elnahas and Tarek M. Ibrahim
Pharmaceuticals 2025, 18(7), 972; https://doi.org/10.3390/ph18070972 - 27 Jun 2025
Viewed by 443
Abstract
Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. [...] Read more.
Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation. Full article
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19 pages, 8480 KiB  
Article
(W/O/W) Double Emulsions-Filled Chitosan Hydrogel Beads for Topical Application
by Rui Sun, Yufeng Sun, Xiaoyan Tang and Juling Ji
Gels 2025, 11(7), 504; https://doi.org/10.3390/gels11070504 - 27 Jun 2025
Viewed by 394
Abstract
The aim of this study was to develop double emulsions-filled chitosan hydrogel beads for topical application and to elucidate their skin penetration behavior. Double emulsions were prepared by a two-step emulsification method, and double emulsions-filled chitosan hydrogel beads were prepared by the extrusion [...] Read more.
The aim of this study was to develop double emulsions-filled chitosan hydrogel beads for topical application and to elucidate their skin penetration behavior. Double emulsions were prepared by a two-step emulsification method, and double emulsions-filled chitosan hydrogel beads were prepared by the extrusion method. The structure, stability, and skin penetration behavior were investigated. The results of yield efficiency (above 80%) and microstructure observation confirmed the feasibility of the preparation method. After loading the hydrophilic active ingredients (vitamin C) into this system, the retention ratio after storage for 6 weeks increased by 77.6%. Furthermore, hydrogel beads could promote the permeation of hydrophilic active ingredients loaded in double emulsions. When the concentration of chitosan was 3% (w/v), the permeation coefficient of vitamin C from hydrogel beads exhibited an increase (1.7-fold) compared with double emulsions. This system could affect the orderliness of lipid structures in the stratum corneum. In addition, the results indicated that this system could be used for the topical delivery of hydrophobic active ingredients (quercetin) as well. This is the first report of chitosan bead stabilization of W/O/W emulsions, yielding a 2.6-fold increase in skin uptake of hydrophilic actives. Full article
(This article belongs to the Special Issue Recent Advances in Gels for Pharmaceutical Application)
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12 pages, 228 KiB  
Review
Acetyl Hexapeptide-8 in Cosmeceuticals—A Review of Skin Permeability and Efficacy
by Julita Zdrada-Nowak, Agnieszka Surgiel-Gemza and Magdalena Szatkowska
Int. J. Mol. Sci. 2025, 26(12), 5722; https://doi.org/10.3390/ijms26125722 - 14 Jun 2025
Viewed by 2534
Abstract
Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received [...] Read more.
Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects—particularly the peptide’s ability to inhibit muscle contraction when applied topically—remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8’s low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments. Full article
23 pages, 4522 KiB  
Article
Betulinic Acid-Loaded Oleogel as a Novel Pharmaceutical Formulation for Potential Cutaneous Applications: Development, Characterization, and Biosafety Profile
by Andreea Smeu, Daliana Minda, Casiana Boru, Lavinia Vlaia, Vicențiu Vlaia, Cristina Adriana Dehelean, Sergio Liga, George Puenea and Daniela Lucia Muntean
Life 2025, 15(6), 954; https://doi.org/10.3390/life15060954 - 13 Jun 2025
Viewed by 587
Abstract
Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due [...] Read more.
Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due to its lipophilic nature and low bioavailability, topical delivery systems are necessary for its proper administration. Oleogels are efficient carriers for the incorporation of hydrophobic biomolecules; however, their use for the delivery of BA remains scarce. Therefore, this study was designed to develop, characterize, and evaluate a BA-containing oleogel (BA-O) regarding its cutaneous safety profile as a potential pharmaceutical formulation targeting dermatologic issues. The findings illustrated the efficient formulation of BA as oleogel, the product presenting the specific conditions of topical semi-solid formulations in terms of physico-chemical characteristics and high biocompatibility in vitro and in ovo, as BA-O lacked a cytotoxic effect in HaCaT and JB6 Cl 41-5a skin cells (cell viability percentages being > 70%) and was categorized as non-irritant in EpiDerm™ tissues (viability > 80%) and on the chorioallantoic membrane (Irritation Score = 0.186). These results present the preclinical biosafety profile of BA-O with prospective potential for cutaneous applications that should be investigated in future studies. Full article
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25 pages, 3318 KiB  
Review
Solute–Vehicle–Skin Interactions and Their Contribution to Pharmacokinetics of Skin Delivery
by Pronalis Tapfumaneyi, Khanh Phan, Yicheng Huang, Kewaree Sodsri, Sarika Namjoshi, Howard Maibach and Yousuf Mohammed
Pharmaceutics 2025, 17(6), 764; https://doi.org/10.3390/pharmaceutics17060764 - 10 Jun 2025
Viewed by 3040
Abstract
Human skin provides an effective route of delivery for selected drugs. Topical penetration of molecules is largely attributed to passive diffusion, and the degree of penetration can be represented by in silico, in vitro, and ex vivo models. Percutaneous absorption of pharmaceutical ingredients [...] Read more.
Human skin provides an effective route of delivery for selected drugs. Topical penetration of molecules is largely attributed to passive diffusion, and the degree of penetration can be represented by in silico, in vitro, and ex vivo models. Percutaneous absorption of pharmaceutical ingredients is a delicate balance between the molecular properties of the drug, the skin properties of the patients, and the formulation properties. Understanding this interplay can aid in the development of products applied to the skin. The kinetics of percutaneous absorption and an understanding of the rate-limiting steps involved can facilitate the optimization of these systems and enhance the degree to which skin drug delivery can be achieved. Solute–vehicle, vehicle–skin, and solute–skin interactions contribute notably to product release as well as the rate of absorption and diffusion across skin layers. These interactions alter the degree of permeation by interfering with the skin barrier or solubility and thermodynamic activity of the active pharmaceutical ingredient. This article aims to provide a concise understanding of some of the factors involved in the skin absorption of topical products, i.e., the pharmacokinetics of percutaneous absorption as well as the solute–vehicle–skin interactions that determine the rate of release of products and the degree of drug diffusion across the skin. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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17 pages, 2031 KiB  
Review
Protein Kinase CK2 Inhibition Represents a Pharmacological Chance for the Treatment of Skin Diseases
by Michele Scuruchi, Desirèe Speranza, Giuseppe Bruschetta, Federico Vaccaro, Mariarosaria Galeano, Giovanni Pallio, Mario Vaccaro, Francesco Borgia, Federica Li Pomi, Massimo Collino and Natasha Irrera
Int. J. Mol. Sci. 2025, 26(11), 5404; https://doi.org/10.3390/ijms26115404 - 4 Jun 2025
Viewed by 650
Abstract
Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and [...] Read more.
Protein kinase CK2 has emerged as a pivotal regulator of cellular processes involved in skin homeostasis, including cell proliferation, differentiation and inflammatory response regulation. In fact, CK2 activity dysregulation is implicated in the pathogenesis of different skin diseases, such as psoriasis, cancer and inflammatory dermatoses. CK2 overactivation fosters keratinocyte proliferation and pro-inflammatory cytokine production through the STAT3 and Akt pathways in psoriasis, thus contributing to epidermal hyperplasia and inflammation. In the realm of oncology, CK2 overexpression correlates with tumor progression, facilitating cell survival and metastasis in melanoma and non-melanoma skin cancers. Pharmacological inhibition of CK2 has demonstrated therapeutic potential, with CX-4945 (Silmitasertib) as the most studied adenosine triphosphate-competitive inhibitor (ATP-competitive inhibitor). Preclinical models reveal that CK2 inhibitors effectively mitigate pathological features of psoriasis, regulate keratinocyte differentiation, and suppress tumor growth in skin cancers. These inhibitors also potentiate the efficacy of conventional chemotherapeutics and exhibit anti-inflammatory effects in dermatological conditions. Future research will aim to enhance the specificity and delivery of CK2-targeting therapies, including topical formulations, to minimize systemic side effects. Combination therapies integrating CK2 inhibitors with other agents might offer synergistic benefits in managing skin diseases. This review underscores CK2’s critical role in skin and its therapeutic potential as a pharmacological target, advocating for innovative approaches to harness CK2 inhibition in dermatology. Full article
(This article belongs to the Special Issue The Role of Protein Kinase in Health and Diseases)
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