Topical retinoids: Novel derivatives, nano lipid-based carriers, and combinations to improve chemical instability and skin irritation.

BACKGROUND: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti-aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products. AIM: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges. METHODS: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid-based carriers, liposomes, penetration-enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed. RESULTS: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid-based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family. CONCLUSIONS: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid-based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods.

[Corrigendum] All­trans retinoic acid alters the expression of the tight junction proteins Claudin­1 and ­4 and epidermal barrier function­associated genes in the epidermis.

Following the publication of the above article, the authors contacted the Editorial Office to explain that they had identified a pair of duplicate images in the control (Vehicle) group of mouse images in Fig. 1A on p. 1792. Specifically, the same image (corresponding correctly to the 'Day 5' experiment) was inadvertently chosen to represent the cutaneous manifestations of mice in the Vehicle group on 'Day 3' and 'Day 5' in Fig. 1A. This error arose as a consequence of repetitive application and duplication procedures within the image set, resulting in the inadvertent reuse of the same photo. Additionally, due to minimal alterations observed in the skin condition of mice from the control group following treatment, each mouse exhibited a similar appearance; this similarity further contributed to the delayed identification of this error during the paper revision stage. Consequently, this duplication of the same image was made as a result of insufficient scrutiny. The revised version of Fig. 1, showing the correct image for the 'Day 3' experiment in Fig. 1A, is shown on the next page. The authors can confirm that the error associated with the assembly of this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 1789­1805, 2019; DOI: 10.3892/ijmm.2019.4098].

Research progress in the development of 3D skin models and their application to in vitro skin irritation testing.

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.

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

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

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model.

AIM: The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. METHOD: Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. RESULT: The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, -27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. CONCLUSION: Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Carboxymethyl cellulose-based rotigotine nanocrystals-loaded hydrogel for increased transdermal delivery with alleviated skin irritation.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson's disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation. RTG-loaded NS-HG was prepared using a bead-milling technique, employing sodium carboxylmethyl cellulose (Na.CMC) as nano-suspending agent (molecular weight 90,000 g/mol) and hydrogel matrix (700,000 g/mol), respectively. NS-HG was embodied as follows: drug loading: ≤100 mg/mL; shape: rectangular crystalline; crystal size: <286.7 nm; zeta potential: -61 mV; viscosity: <2.16 Pa·s; and dissolution rate: >90 % within 15 min. Nuclear magnetic resonance analysis revealed that the anionic polymers bind to RTG nanocrystals via charge interaction, affording uniform dispersion in the matrix. Rodent transdermal absorption of RTG from NS-HG was comparable to that from microemulsions, and proportional to drug loading. Moreover, NS-HG was skin-friendly; erythema and epidermal swelling were absent after repeated application. Further, NS-HG was chemically stable; >95 % of the drug was preserved up to 4 weeks under long term (25 °C/RH60%), accelerated (40 °C/RH75%), and stress (50 °C) storage conditions. Therefore, this novel cellulose derivative-based nanoformulation presents a promising approach for effective transdermal RTG delivery with improved tolerability.

Incorporation of Resveratrol-Hydroxypropyl-ß-Cyclodextrin Complexes into Hydrogel Formulation for Wound Treatment.

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-ß-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-ß-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy.

Reference chemical database for the development and validation of in vitro alternatives to skin irritation and comparison of the performance of RhE models.

After EU ban on animal testing for cosmetics in 2013, there has been an increasing global interest in alternatives test methods. To development for alternatives test method, we need to get the toxic data about in vitro and in vivo of chemicals. However, database sometimes provide limited in vivo and in vitro data on chemicals. Further, the data generated using the OECD TG439 (in vitro skin irritation) are scattered in difference databases, and it is not easy to navigate through them. Therefore, we complied 'Reference Chemical Database System for Skin Irritation Alternative Test (RCDS-Skin Irritation)' to allow easy, one-stop access to test chemical information. We established the systematic RCDS-Skin Irritation by collecting physiochemical properties, CAS number, human data, and in vivo (OECD TG404) data from overseas chemicals database including European Chemicals Agency (ECHA) etc., and in vitro data using Reconstructed human Epidermis (RhE) (OECD TG439). As a result, we developed the RCDS-Skin Irritation that contains information on 149 chemicals including the data we generated by performing tests using EpiDerm™ SIT, SkinEthic™ RHE and KeraSkin™ SIT. Therefore, the RCDS-Skin Irritation established based on our study will provide insight for safety assessment of chemicals and for development of alternative test methods.

Effect of Ducrosia anethifolia methanol extract against methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms on excision wound in diabetic mice.

Background: Ducrosia anethifolia is an aromatic desert plant used in Saudi folk medicine to treat skin infections. It is widely found in Middle Eastern countries. Methods: A methanolic extract of the plant was prepared, and its phytoconstituents were determined using LC-MS. In-vitro and in-vivo antibacterial and antibiofilm activities of the methanolic extract were evaluated against multidrug-resistant bacteria. The cytotoxic effect was assessed using HaCaT cell lines in-vitro. Diabetic mice were used to study the in-vivo antibiofilm and wound healing activity using the excision wound method. Results: More than 50 phytoconstituents were found in the extract after LC-MS analysis. The extract exhibited antibacterial activity against both the tested pathogens. The extract was free of irritant effects on mice skin, and no cytotoxicity was observed on HaCaT cells with an IC50 value of 1381 µg/ml. The ointment formulation of the extract increased the healing of diabetic wounds. The microbial load of both pathogens in the wounded tissue was also reduced after the treatment. The extract was more effective against methicillin-resistant Staphylococcus aureus (MRSA) than MDR-P. aeruginosa in both in vitro and in vivo experiments. Further, skin regeneration was also observed in histological studies. Conclusions: The results showed that D. anethifolia methanol extract supports wound healing in infected wounds in diabetic mice through antibacterial, antibiofilm, and wound healing activities.

Photodegradation enhances the toxic effect of anthracene on skin.

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.

3D Bioprinted Human Skin Model Recapitulating Native-Like Tissue Maturation and Immunocompetence as an Advanced Platform for Skin Sensitization Assessment.

Physiologically-relevant in vitro skin models hold the utmost importance for efficacy assessments of pharmaceutical and cosmeceutical formulations, offering valuable alternatives to animal testing. Here, an advanced immunocompetent 3D bioprinted human skin model is presented to assess skin sensitization. Initially, a photopolymerizable bioink is formulated using silk fibroin methacrylate, gelatin methacrylate, and photoactivated human platelet releasate. The developed bioink shows desirable physicochemical and rheological attributes for microextrusion bioprinting. The tunable physical and mechanical properties of bioink are modulated through variable photocuring time for optimization. Thereafter, the bioink is utilized to 3D bioprint "sandwich type" skin construct where an artificial basement membrane supports a biomimetic epidermal layer on one side and a printed pre-vascularized dermal layer on the other side within a transwell system. The printed construct is further cultured in the air-liquid interface for maturation. Immunofluorescence staining demonstrated a differentiated keratinocyte layer and dermal extracellular matrix (ECM)-remodeling by fibroblasts and endothelial cells. The biochemical estimations and gene-expression analysis validate the maturation of the printed model. The incorporation of macrophages further enhances the physiological relevance of the model. This model effectively classifies skin irritative and non-irritative substances, thus establishing itself as a suitable pre-clinical screening platform for sensitization tests.

Anti-UV Microgel Based on Interfacial Polymerization to Decrease Skin Irritation of High Permeability UV Absorber Ethylhexyl Methoxycinnamate.

Ethylhexyl methoxycinnamate (EHMC) is frequently employed as a photoprotective agent in sunscreen formulations. EHMC has been found to potentially contribute to health complications as a result of its propensity to produce irritation and permeate the skin. A microgel carrier, consisting of poly(ethylene glycol dimethacrylate) (pEDGMA), was synthesized using interfacial polymerization with the aim of reducing the irritation and penetration of EHMC. The thermogravimetric analysis (TGA) indicated that the EHMC content accounted for 75.72% of the total composition. Additionally, the scanning electron microscopy (SEM) images depicted the microgel as exhibiting a spherical morphology. In this study, the loading of EHMC was demonstrated through FTIR and contact angle tests. The UV resistance, penetration, and skin irritation of the EHMC-pEDGMA microgel were additionally assessed. The investigation revealed that the novel sunscreen compound, characterized by limited dermal absorption, had no irritant effects and offered sufficient protection against ultraviolet radiation.

Development of Curcumin and Turmerone Loaded Solid Lipid Nanoparticle for Topical Delivery: Optimization, Characterization and Skin Irritation Evaluation with 3D Tissue Model.

Background: Curcuma longa L., commonly known as turmeric, is renowned for its therapeutic benefits attributed to bioactive compounds, namely curcumin (Cur) and aromatic turmerone (Tur), present in its rhizome. These compounds exhibit diverse therapeutic properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, the topical application of these compounds has a significant potential for inducing skin irritation. This study focuses on formulating solid lipid nanoparticle (SLN) carriers encapsulating both Cur and Tur for reduced irritation and enhanced stability. Methods: SLN formulations were prepared by a method using homogenization followed by ultrasonication procedures and optimized by applying response surface methodology (RSM). Results: The optimized SLN formulation demonstrated entrapment efficiencies, with 77.21 ± 4.28% for Cur and 75.12 ± 2.51% for Tur. A size distribution of 292.11 ± 9.43 nm was obtained, which was confirmed to be a spherical and uniform shape via environmental scanning electron microscopy (ESEM) images. The in vitro release study indicated cumulative releases of 71.32 ± 3.73% for Cur and 67.23 ± 1.64% for Tur after 24 hours under sink conditions. Physical stability tests confirmed the stability of formulation, allowing storage at 4°C for a minimum of 60 days. Notably, in vitro skin irritation studies, utilizing the reconstructed human epidermal model (EPI-200-SIT), revealed a significant reduction in irritation with the SLN containing Cur and Tur compared to nonencapsulated Cur and Tur. Conclusion: These findings collectively endorse the optimized SLN formulation as a favorable delivery system for Cur and Tur in diverse topical uses, offering enhanced stability, controlled release and reduced irritation.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

In vitro and Ex vivo study targeting the development of a Lavandula stoechas L. (Ustukhuddus) loaded Unani Transdermal patch: Implication of Unani Medicine in the treatment of Nisyan (Dementia).

Ustukhuddus (Lavandula stoechas L.) has been extensively used orally and topically in treating various neurological disorders, including dementia. The optimum potential of traditional dosage forms of Ustukhuddus is limited for various reasons. Transdermal drug delivery system (TDDS) is a novel means of drug delivery and is known to overcome the drawbacks associated with traditional dosage forms. The current study aimed at fabricating and evaluating Ustukhuddus hydro-alcoholic extract (UHAE) and essential oil (UEO) loaded matrix-type transdermal patches having a combination of hydrophilic - hydroxyl propyl methyl cellulose (HPMC) and hydrophobic - ethyl cellulose (EC) polymers. ATR-FTIR, DSC, XRD, and SEM analysis were carried out to study drug-polymer interactions, confirming the formation of developed patches and drug compatibility with excipients. We assessed the fabricated patches to evaluate their physicochemical properties, in vitro drug release, and permeation characteristics via ex vivo experiments. The physicochemical characteristics of patches showcased the development of good and stable films with clarity, smoothness, homogeneity, optimum flexibility and free from causing skin irritancy or sensitization. In vitro drug release and ex vivo permeation profile of developed patches were evaluated employing Franz diffusion cells. UHAE and UEO patches exhibited a cumulative drug release of 81.61 and 85.24 %, respectively, in a sustained-release manner and followed non-Fickian release mechanisms. The ex vivo permeation data revealed 66.82 % and 76.41 % of drug permeated from UHAE and UEO patches, respectively. The current research suggests that the formulated patches are more suitable for TDDS and hold potential significance in the treatment of dementia, contributing to enhanced patient compliance, thereby highlighting the implication of Unani Medicine in Nisyan (Dementia) treatment.

Safety-in-use test of facial cosmetic products on normal and self-assessed sensitive skin subjects.

BACKGROUND: Safety-in-use (SIU) studies are commonly used by the cosmetic Industry to confirm the skin and ocular compatibility of cosmetic products under realistic in-use conditions. There are only limited case studies published about the design, outcome and interpretation of product SIU studies. OBJECTIVE: A series of SIU case studies is presented to demonstrate the considerations in study design and how the methodology can help in supporting skin and ocular safety profile of facial cosmetic products within a population of different ethnicities with normal and self-perceived sensitive skin. SUBJECTS/METHODS: In a series of four single-blinded SIU studies, more than 250 female study subjects of different ethnicities and with normal and self-assessed sensitive skin were asked to use different facial cosmetic products including lotions, essences and cleansers according to the instructed usage conditions of these products. Each study was specifically designed according to product usage scenarios and target consumer groups. The primary measures of safety were based on dermal evaluations by a dermatologist for erythema and dryness/scaling and by an ophthalmologist for any visible signs of an ocular condition on eyelids, conjunctivae and cornea. The study subjects were also asked for any self-perceived skin or eye reactions. Dermal and ocular irritation potential of the products under realistic product usage conditions was evaluated according to the measures. RESULTS: Across all studies, objectively and self-assessed mean scores for skin and eye effects did not indicate any cumulative response of the investigated products over the study period. CONCLUSIONS: As a suitable tool for assessing and establishing the skin and eye compatibility of facial cosmetic products, SIU studies can be designed according to specific consumer groups, skin types and product usage scenarios to better predict realistic in-use conditions. It can demonstrate the safe use of the investigated products for people of different ethnicities, skin types and with normal or self-assessed sensitive skin, single product use or regimen use. The test results are consistent with the inherently low irritation potential of the products.

The effect of electrical stimulation on skin vulnerability to irritants.

PURPOSE: Electrical stimulation (ES) is a widely used technique in the medical field for various purposes. The effect of ES on several skin properties has been investigated; however, its effect on skin vulnerability to irritants remains unknown. This study aimed to investigate the effects of ES application on skin vulnerability to external irritants. MATERIALS AND METHODS: An experimental study on 12 healthy male subjects (Mean ± SD, 22.9 ± 3.6 years) who completed the study. The subjects were free of skin abnormalities in the volar aspect of both forearms. Three areas were allocated to each forearm and marked as areas 1, 2, and A in the treated forearm, and areas 3, 4, and B in the control forearm. ES was applied to the volar aspect of the treated forearm for 30 min three times a week, for 2 weeks. The effect of ES on skin vulnerability was investigated using 5% and 0.5% sodium lauryl sulfate (SLS) patches applied to both treated and control forearms. The skin response to irritants was evaluated using transepidermal water loss (TEWL) and a visual erythema score 24 h after patch removal. RESULTS: Compared to the control forearm, ES increased skin permeability and erythema in response to external irritants (SLS), as measured by the visual analog score (Z = 2.75, p = 0.006) and TEWL (p < 0.05), respectively. CONCLUSIONS: ES escalates skin reactions to low concentrations of irritant substances, such as SLS, in the area between the two electrodes. This emphasizes the use of this substance, and similar irritants should be avoided in areas treated with ES.

QbD-assisted optimisation of liposomes in chitosan gel for dermal delivery of aceclofenac as synergistic approach to combat pain and inflammation.

Aceclofenac (ACE) is a drug that was precisely devised to circumvent the shortcomings associated with diclofenac. However, ACE too corresponds to nonsteroidal anti-inflammatory drug (NSAID)-related adverse effects, but with a lower amplitude. The present investigation seeks to develop liposomes loaded with ACE adopting a central composite design (CCD) and formulate a chitosan-based hydrogel for synergistic anti-inflammatory efficacy and improved ACE dermal administration. On the basis of preliminary vesicle size, Poly Dispersity Index (PDI), and drug entrapment, the composition of lipid, cholesterol, and vitamin E TPGS were chosen as independent variables. The formulation composition met the specifications for an optimum liposomal formulation, with total lipid concentration (13.5% w/w), cholesterol concentration (10% w/w), and surfactant concentration (2% w/w). With particle size and PDI of 174.22 ± 5.46 nm and 0.285 ± 0.01 respectively, the optimised formulation achieved an entrapment effectiveness of 92.08 ± 3.56%. Based on the CCD design, the optimised formulation Acec-Lipo opt was chosen and was subsequently transformed to a chitosan-based gel formulation for in vitro drug release, penetration through the skin, in vivo analgesic therapeutic activity, and skin irritation testing. % age oedema inhibition was found to be greatest with the Acec-Lipo opt gel formulation, followed by Acec gel. These results reinforce the notion that the inclusion of chitosan resulted in a synergistic effect despite the same strength of the drug. The findings suggested that Acec-Lipo incorporated in chitosan gel for skin targeting might be an effective formulation for topical ACE administration in clinical subjects.

Multispectral near-infrared spectroscopy study evaluating the effect of razor design on shaving-induced erythema.

BACKGROUND: While shaving-induced erythema is a common inflammatory skin issue, there is a lack of quantitative information on how well a shaving product performs in this regard. In this study, multispectral near-infrared spectroscopy (NIRS) imaging was used to quantitatively and qualitatively measure the extent of shaving-induced erythema. The research compares a safety razor and a cartridge razor to evaluate their impact on skin irritation. MATERIALS AND METHODS: Fifty-nine healthy male volunteers without pre-existing skin conditions were enrolled. Basic demographics were recorded, and participants' faces or necks were imaged before shaving. Shaving was conducted on the right side of the face/neck with the safety razor and on the left side of the face/neck using the 3-blade cartridge razor. Images were captured immediately after shaving, at 5 and 10 min post-shaving. RESULTS: Tissue oxygen saturation (StO2) measurements demonstrated that the safety razor induced significantly less erythema than the cartridge razor. Immediately after shaving, 40.3% of skin shaved with the safety razor had erythema compared to 57.6% for the cartridge razor. At 5 min post-shaving, 36.5% of skin shaved with the safety razor had erythema, compared to 53.8% of cartridge razor. CONCLUSIONS: Multispectral NIRS revealed significant differences in shaving-induced erythema between safety and cartridge razors. Safety razors demonstrated a lower incidence of erythema, suggesting a potential advantage for individuals prone to skin irritation. This study contributes valuable insights into skin irritation and highlights the potential of multispectral NIRS in dermatology research.

A comparative study on the effect of alcohol-based hand sanitizers in spray and gel formulation on the skin: A prospective, randomised, crossover trial.

BACKGROUND: Many formulations of Alcohol-based hand rubs (ABHRs), such as liquid, gel, and spray have been developed and used for preventing infections. This study aimed to compare skin irritation from using ABHRs in gel and spray formulations. METHOD: This was a prospective, randomised, crossover trial conducted to investigate the effect of skin irritation caused by ABHRs in gel compared to spray formulation after 21 days of using each formulation. Clinical outcomes were assessed using subjective Larson's skin assessment score and Frosch and Kligman observer skin assessment score, as well as bioengineering measures: transepidermal water loss (TEWL) and skin capacitance on days 3, 7, 14, and 21. RESULTS: Among 38 participants, both formulations showed no significant change in clinical scores and skin capacitance during the study. However, TEWL increased significantly from baseline on day 3 (p = 0.029) for the spray formulation and on day 21 (p = 0.019) for the gel formulation, with no statistically significant difference between the formulations (p = 0.46). CONCLUSION: Our research supports the safety of gel and spray ABHRs for regular use, with the only potential issue being mild skin irritation. For those with sensitive skin, the gel formulation is preferable.