Search Results (131)

Prunus leaf extracts are rich in phenolic and flavonoid compounds like rutin, and they are known for their antioxidant potential. This study compares the bioactivity and stability of leaf extracts from Prunus domestica L. (EL), Prunus salicina Lindl. (JL), and Prunus cerasifera Ehrh. (CL) and evaluates the dermal safety of a cream containing the extract with the most favorable in vitro properties for potential cosmetic use. Ethanolic extracts were assessed for total phenolic and condensed tannin contents, as well as antioxidants, using DPPH assay and lipid peroxidation inhibitory activities. The CL extract exhibited moderate total phenolic content, the highest condensed tannin content, and strong antioxidant (IC₅₀ = 22.1 ± 3.1 µg/mL) and anti-lipid peroxidation (62.3 ± 1.0%) activities. Based on these results, CL was incorporated into a cream formulation (CCL), which was then evaluated for physicochemical properties, antioxidant retention, and in vitro skin permeation using Franz diffusion cells. The formulation remained physically stable under ambient conditions and retained antioxidant activity above 74.5% under thermal cycling conditions. Rutin from the CCL formulation was retained within the Strat-M™ membrane (4.0 ± 1.1%), which was 5.7-fold higher than that of the control (0.7 ± 0.6%) over 8 h; however, it was not detected in the receptor chamber under these in vitro conditions. A semi-open patch test conducted on 26 healthy volunteers under double-blind conditions revealed no signs of irritation, confirming the formulation’s dermal safety. Overall, the findings support the feasibility of using P. cerasifera extract as a stable antioxidant component in topical skincare formulations. Full article

Background/Objectives: This study investigates the physical, rheological, and antioxidant properties of nano-liposomal formulations encapsulating Fumaria officinalis L. (fumitory) extract, focusing on their stability and performance under ultraviolet (UV) exposure, as well as polyphenol release within simulated skin conditions in a Franz diffusion cell. Methods: Liposomal formulations, composed of phospholipids with or without β-sitosterol or ergosterol, were evaluated for their encapsulation efficiency, liposome size, size distribution, zeta potential, viscosity, surface tension, density, oxidative stability, antioxidant capacity, and polyphenol recovery. Results: Encapsulation efficiency was the highest in phospholipid liposomes (72.2%) and decreased with the incorporation of sterols: 66.7% for β-sitosterol and 62.9% for ergosterol liposomes. Encapsulation significantly increased viscosity and reduced surface tension compared to the plain liposomes, suggesting modified interfacial behavior. The inclusion of fumitory extract significantly increased the viscosity of liposomes (from ~2.5 to 6.09–6.78 mPa × s), consistent with the observed reduction in particle size and zeta potential. Antioxidant assays (thiobarbituric acid reactive substances—TBARS, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid—ABTS, and 2,2-diphenyl-1-picrylhydrazyl—DPPH) confirmed enhanced lipid peroxidation inhibition and radical scavenging upon encapsulation, with ABTS activity reaching up to 95.05% in sterol-containing liposomes. Release studies showed that the free extract exhibited the fastest polyphenol diffusion (5.09 × 10⁻⁹ m²/s), while liposomes demonstrated slower/controlled release due to bilayer barriers. UV-irradiated liposomes released more polyphenols than untreated ones, particularly in the sterol-containing formulations, due to oxidative destabilization and pore formation. Conclusions: These findings highlight the potential of fumitory extract-loaded liposomes as stable, bioactive carriers with tunable polyphenol antioxidant release properties for dermal applications. Overall, liposomal formulations of fumitory extract exhibit significant potential for further development as a pharmaceutical, cosmetic, or dermo-cosmetic ingredient for use in the prevention and treatment of various skin disorders. Full article

Background: Tuberculosis remains a significant global health issue, and the rise of drug-resistant strains is becoming increasingly concerning. Currently, treatment options are limited to systemic regimens; however, developing topical drug delivery systems could offer advantages for treating cutaneous tuberculosis (CTB) when applied directly to the lesions. We developed topical emulsions using the self-emulsification mechanism that combine fixed doses of isoniazid (INH) and rifampicin (RIF) using a quality-by-design approach. Methods: Preformulation studies pertaining to drug solubility in various solvents, the construction of pseudoternary diagrams to identify self-emulsification regions for each tested excipient combination, and the preparation of checkpoint formulations were conducted and visually examined. Formulations displaying no physical instabilities were subsequently exposed to characterization experiments, including droplet size determination, zeta potential, size distribution, viscosity, pH, self-emulsification, cloud point, robustness to dilution, and thermodynamic stability assessment. Three selected formulations were consequently subjected to membrane release experiments, followed by skin diffusion studies, and INH and RIF stability in these emulsions was determined, because these drugs have a known interaction. Conclusions: While incorporating essential oils in a topical formulation improved RIF solubility, it also resulted in several instabilities. RIF exhibited greater susceptibility to degradation under higher temperatures and lower pH conditions. However, drug release from all formulations tested was confirmed. Notably, olive oil microemulsions demonstrated the most favorable characteristics for dermal drug delivery; nonetheless, drug diffusion into and through the skin (which was not desired) could not be quantified. Despite these challenges, the findings indicate that topical drug delivery systems using the self-emulsification process can facilitate the direct treatment of CTB. Full article

Background/Objective: This study provided a comparison of the influence of each component of the microemulsion formulation and investigated the impact of varying concentrations of the microemulsion components on curcumin’s ability to penetrate the skin using an ex vivo porcine ear model. Methods: Curcumin microemulsions with different compositions were prepared and analyzed for their physicochemical properties. The dermal penetration efficacy of curcumin was evaluated from the different formulations and compared with non-microemulsion formulations. Results: Findings proved that microemulsion formulations improve the dermal penetration efficacy for curcumin when compared with non-microemulsion formulations. The composition of the microemulsion affects the penetration efficacy of curcumin and increases with decreasing oil content and increasing surfactant and water content. The best penetration for curcumin is achieved with a microemulsion that contained 7.7 g of medium-chain triglycerides as the oil phase, 6.92 g of Tween^® 80 and 62.28 g of ethanol as the surfactant mixture, and 23.1 g water. Conclusions: The present study provides a foundational basis for further development of different microemulsion formulations for enhancing the dermal penetration of poorly water-soluble active compounds. Full article

Tattoo inks contain varying amounts of metal nanoparticles (NPs) < 100 nm that, due to their unique physicochemical properties, may have specific biological uptake and cause skin or systemic toxicities. The toxic effects of certified reference standards of metal NPs and samples of commercially available tattoo inks were investigated using an in vitro system and a novel human ex vivo model. In vitro toxicity was evaluated using vitality assays on human skin cells (HaCaT cell line, primary fibroblasts, and keratinocytes). No toxicity was observed for Al₂O₃, Cr₂O₃, Fe₂O₃, and TiO₂ NPs, whereas CuO NPs showed dose-dependent toxicity on HaCaT and primary fibroblasts. Fibroblasts and keratinocytes were also sensitive to high concentrations of ZnO NPs. Reference standards and ink samples were then injected ex vivo into human skin explants using tattoo needles. Histological analysis showed pigment distribution deep in the dermis and close to dermal vessels, suggesting possible systemic diffusion. The presence of an inflammatory infiltrate was also observed. Immunohistochemical analysis showed increased apoptosis and expression of the inflammatory cytokine interleukin-8 in explants specifically tattooed with the reference standard or red ink. Taken together, the results suggest that the tattooing technique leads to exposure to toxic metal NPs and skin damage. Full article

Skin aging is accelerated by inflammation processes generated by oxidative stress and external factors such as UV radiation. Plants belonging to the genus Kalanchoe that are rich sources of antioxidants could potentially strengthen the skin barrier if used as ingredients in cosmetic formulations. However, their use is limited due to the contents of bufadienolides, known cardiotoxins. This study aimed to establish a semi-quantitative profile of bufadienolides in the juices of K. blossfeldiana, K. daigremontiana, and K. pinnata using UHPLC combined with charged aerosol detection (CAD) and high-resolution mass spectrometry (HR-MS). Additionally, the study determined the ability of bufadienolides to penetrate the skin barrier using the Bronaugh Diffusion Cell Apparatus and Strat-M membrane. The study also assessed the ferric and molybdenum-reducing powers, as well as the radical scavenging capabilities of these plants juices using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) methods. The in vitro antihyaluronidase and antityrosinase activities and sun protection factor (SPF) were evaluated spectrophotometrically, indicating moderate capability to inhibit the skin enzymes, but low SPF protection for all analyzed juices. The semi-qualitative analysis demonstrated the presence of bufadienolides occurring in two juices from K. daigremontiana and K. pinnata, with the highest contents of 1,3,5-bersaldegenin-orthoacetate, bryophyllin-A/bryotoxin-C, bersaldegenin-acetate/bryophyllin-C, and diagremontianin. After passing through the skin model, no bufadienolide compounds were present in the subcutaneous filtrate. Antiradical and reduction assays revealed the antioxidant potential of K. blossfeldiana and K. pinnata. These results indicate that Kalanchoe juices have antiaging potential and appear safe for dermal applications. Full article

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G′ values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN’s composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9–1), depending on the IPN’s composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells. Full article

The rapid development of the global chemical industry has led to widespread groundwater contamination, with frequent pollution incidents posing severe threats to water safety. However, there has been insufficient assessment of the health risks posed by chlorinated hydrocarbon contamination in groundwater around chemical industrial parks. This study evaluates the chlorinated hydrocarbon contamination in groundwater at a chemical park and conducts a multi-pathway health risk assessment, identifying the key risk pollutants. In addition, sensitivity analysis of the primary exposure pathways was performed using the Monte Carlo method. The results indicate severe exceedance of pollutant concentrations with widespread diffusion. Carcinogenic risks were mainly driven by vinyl chloride, whose oral cancer slope factor was significantly higher than that of other substances, while non-carcinogenic risks were dominated by trichloro-ethylene, which had the lowest reference dose. Both carcinogenic and non-carcinogenic risks through the drinking water pathway accounted for approximately 90% of the total risk, whereas the risk contribution from dermal contact was negligible. Although boiling water can partially reduce the risks, its effect on high-concentration pollutants is limited. Additionally, sensitivity analysis showed that pollutant concentration was the primary influencing factor for risk values, followed by exposure duration. The findings of this study provide a scientific basis for effectively formulating pollution control measures and ensuring the drinking water safety of nearby residents. Full article

One of the major challenges in dermal drug delivery is the adequate penetration of the active compound into the skin without causing any skin irritation and inflammation. Nanocrystals (NCs) are nanoscale particles, and their sizes are below 1000 nm. NCs are made up of drug particles only, which are used to improve the aqueous solubility and bioavailability of poorly water-soluble drugs. NCs are typically prepared either by bottom-up or top-down techniques. The advantages of using NC-based formulations in enhancing dermal drug delivery include increased drug loading capacity, easier and deeper penetration into the skin tissue, and increased passive diffusion. NC-based formulations with the capacity of enhanced dermal drug delivery can be effectively used to treat a wide range of skin disorders, including melanoma, inflammation, psoriasis, acne vulgaris, bacterial infections, fungal infections, eczema, skin aging, herpes simplex virus infections, skin manifestations of tick bites, frostbite-related infections, hyperpigmentation, and diabetic foot ulcer. In this review, major challenges in dermal drug delivery across the skin barrier, mechanism of action of dermal NCs, advantages of using NCs in enhancing dermal drug delivery, NC preparation methods, and applications of NCs in the treatment of various skin disorders have been discussed. Full article

Successful skin wound healing is dependent on an interplay between epidermal keratinocytes and dermal fibroblasts as they react to local extracellular factors (DAMPs, PAMPs, cytokines, etc.) surveyed from that environment by numerous membrane receptors (e.g., TLRs, cytokine receptors, etc.). In turn, those receptors are the start of a cytoplasmic signaling pathway where balance is key to effective healing and, as needed, cell and matrix regeneration. When directed through NF-κB, these signaling routes lead to transient responses to the benefit of initiating immune cell recruitment, cell replication, local chemokine and cytokine production, and matrix protein synthesis. The converse can also occur, where ongoing canonical NF-κB activation leads to chronic, hyper-responsive states. Here, we assess three key players, TAK1, TNFAIP3, and TNIP1, in cytoplasmic regulation of NF-κB activation, which, because of their distinctive and yet inter-related functions, either promote or limit that activation. Their balanced function is integral to successful wound healing, given their significant control over the expression of inflammation-, fibrosis-, and matrix remodeling-associated genes. Intriguingly, these three proteins have also been emphasized in dysregulated NF-κB signaling central to systemic sclerosis (SSc). Notably, diffuse SSc shares some tissue features similar to an excessive inflammatory/fibrotic wound response without eventual resolution. Taking a cue from certain instances of aberrant wound healing and SSc having some shared aspects, e.g., chronic inflammation and fibrosis, this review looks for the first time, to our knowledge, at what those pathologies might have in common regarding the cytoplasmic progression of NF-κB-mediated signaling. Additionally, while TAK1, TNFAIP3, and TNIP1 are often investigated and reported on individually, we propose them here as three proteins whose consequences of function are very highly interconnected at the signaling focus of NF-κB. We thus highlight the emerging promise for the eventual clinical benefit derived from an improved understanding of these integral signal progression modulators. Depending on the protein, its indirect or direct pharmacological regulation has been reported. Current findings support further intensive studies of these points in NF-κB regulation both for their basic function in healthy cells as well as with the goal of targeting them for translational benefit in multiple cutaneous wound healing situations, whether stemming from acute injury or a dysregulated inflammatory/fibrotic response. Full article

Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a “viral relay” to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4⁺ and CD8⁺ T cells. Full article

Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin. Full article

Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics and the emergence of antibiotic-resistant strains. In a previous study, a chitosan-based matrix crosslinked with tannic acid and loaded with gentamicin was reported. In this study, five different antibiotics (moxifloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole or linezolid) were loaded into these chitosan-based films, and their impact on the release behavior carefully assessed. Methods: The samples were characterized according to their thickness, swelling, and mass loss in phosphate-buffered saline (PBS), as well as by morphology using scanning electron microscopy (SEM) and optical phase contrast microscopy. Antibiotic release over time was quantified in PBS by high-performance liquid chromatography (HPLC). Antibacterial activity was investigated by disk diffusion test and antibiotic release over time. Finally, the cytotoxicity of the samples was assessed with human dermal fibroblasts. Results: The obtained results differed significantly, especially regarding the antibiotic release time and antibacterial activity, which varied from one day to six months, enabling classification of the films from burst/transient to prolonged release. The films also showed antibacterial features against bacteria mostly present in medical devices and displayed to be non-cytotoxic. Conclusions: In conclusion, it was demonstrated that the antibiotics structure significantly alters the release kinetics, and that by carefully selecting the antibiotic, the consequent release can be tuned. This approach yielded films that could be used for potentially-scalable release in antimicrobial coatings specific to medical devices, aiming to reduce biomaterial associated infections (BAIs). Full article

We developed a tailored 3D Agarose-well system integrated with reconstructed human skin equivalents to enhance skin penetration assessments. This system addresses common limitations in traditional trans-well reconstructions, such as dermal layer contraction and limited lateral diffusion, by entangling collagen fibrils within the Agarose-well. We evaluated the penetration behavior of three peptides, with and without skin-penetrating peptide (SPP) sequences, alongside adenosine, a known anti-wrinkle agent. Despite a SPP having a molecular weight approximately four times greater than that of adenosine, its kinetic constant was similar, with values of about 39 and 34, respectively. Moreover, this living skin equivalent system not only allowed for the evaluation of adenosine penetration, but also demonstrated its biological effects, with adenosine significantly enhancing procollagen synthesis by approximately 23% compared to the control. Overall, this novel strategy holds the potential for tailoring 3D Agarose-wells and advancing high-performance gel development, making it a promising approach for applications in tissue engineering, medical science, regenerative medicine, and cosmetics. Full article

Reactive oxygen species (ROS), commonly known as free radicals, induced by UV radiation can compromise the dermal structure, leading to a loss of skin elasticity and subsequent wrinkle formation. A promising strategy to prevent and mitigate skin aging involves the use of topical formulations with potent antioxidant properties. Secondary metabolites such as astaxanthin and zeaxanthin are known for their robust antioxidant activities, which surpass those of tocopherol, offering significant benefits for skin health and protection against UV-induced damage. These properties suggest their potential application in anti-aging products. This study aims to evaluate the stability, ex vivo penetration, and in vivo efficacy of a radiance serum containing an astaxanthin–zeaxanthin nanoemulsion (AZ-NE) designed as an anti-wrinkle agent for topical application. The research was conducted in four stages: production of the astaxanthin–zeaxanthin nanoemulsion (AZ-NE), formulation of the AZ-NE radiance serum, stability, and efficacy testing. In this study, the formulated radiance serum demonstrated stability over three months under specified storage conditions. Ex vivo penetration studies indicated efficient diffusion of the active ingredients, with astaxanthin showing a penetration rate of 25.95%/cm² and zeaxanthin at 20.80%/cm² after 120 min. In vivo irritation tests conducted on human subjects revealed no adverse effects. Moreover, the serum exhibited substantial anti-wrinkle efficacy, with 15 female participants experiencing a wrinkle reduction of 80% to 93% over a 28-day period. Full article