Skin Irritation Test Research Articles

The physical quality test formulation of ethyl acetate extract of kawista fruit peel (Limonia Acidissima L.) Ointment as an antibacterial against propionibacterium acnes

Introduction: Using medicinal plants in Indonesia still needs to be optimized. Almost all parts of the Kawista plant have been traditionally used to treat various ailments such as antioxidants, antidiabetic, wound healing, and controlling uric acid levels. Existing research on Kawista fruit peel as an acne antibacterial includes studies on the ethyl acetate extract of Kawista fruit peel against Propionibacterium acnes, which falls into the moderate to strong category. In Indonesia, Kawista fruit is limited to the flesh and is used to make syrup and dodol (a traditional sweet). In contrast, the fruit's peel remains a waste product. Objective: This study aims to develop a formula for an ethyl acetate extract ointment of Kawista fruit peel (Limonia acidissima L.) as an antibacterial agent against Propionibacterium acnes with good physical quality. Methods: The fruit peel extract was obtained using the maceration method with 96% ethanol. The extract was then formulated into ointment preparations with concentration variations of 6.25% (F1), 12.50% (F2), and 25% (F3). The physical stability tests for the ointment included organoleptic parameters, homogeneity, spreadability, and pH value tests. The data were analyzed to determine the effect of the extract concentration and storage time on the ointment's physical stability. Result: The test results showed that the ointment formulation of Kawista fruit peel extract (Limonia acidissima L.) could be successfully formulated into an ointment form and met the required evaluation criteria, including organoleptic testing, homogeneity testing, pH testing, and spreadability testing. Conclusion: Based on the study, it can be concluded that the Kawista fruit peel extract ointment (Limonia acidissima L.) can be successfully formulated into an ointment and meets the required evaluation criteria, including organoleptic testing, homogeneity testing, pH testing, and spreadability testing. A skin irritation test is required to determine whether any irritation occurs after applying the ointment.

Development of an Ointment to Medicate Medicine for Dosage Caused by Mucus in Babies with the Active Compound Sotong (Sepia sp.) and Essential Oils Cymbopogon citratus

Sumbawa society is rich in culture, especially in traditional medicine. People use materials from the surrounding environment, including plants and animals, as active ingredients for medicine. Newborn babies and toddlers are susceptible to blockage of the respiratory tract with mucus. In babies, it is usually caused by an imperfect suction process, while in toddlers, it is caused by bacteria or viruses. The Samawa people use a mixture of cuttlefish (Sepia sp.) and eucalyptus oil as a medicine that effectively removes mucus from the body. The active ingredient in cuttlefish has an unpleasant odour and cannot be stored for long. When they need cuttlefish, people must look for them in markets or traders on the coast. Of course, this takes time to use. The ointment production innovation has many advantages, including practicality, no fishy smell, ease of obtaining, and ease of storage for the long term. Using the natural active ingredient lemongrass, essential oil adds aromatherapy and provides warmth to the chests of babies and toddlers. Natural active and gel-based ingredients are safe to use without side effects. The ointment was tested for active ingredient content using GCMS and organoleptic tests for gel stability, spreadability (homogeneity), pH, and skin irritation. Based on the description above, it can be concluded that the ointment product is made from an anti-skin irritation gel base, pH 7, and gel spreadability of 5.5 cm. The active substance comes from cuttlefish Sepia sp. by inhibiting the COX-2 enzyme and reducing the production of prostaglandin E2 (PGE2), an essential inflammatory mediator in the pathogenesis of asthma and bronchitis. The simple production process means that the price of the ointment is within people's purchasing power.

Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin

Transdermal drug delivery systems hold promise, but their effectiveness is often constrained by the skin’s barrier. Microneedles (MNs) improve drug permeability by creating micro-channels in the skin, yet they continue to face challenges such as infection risks and safety concerns. To overcome these challenges, a novel antimicrobial sponge MNs (ASMNs@PVP-INS) modified with polyvinylpyrrolidone (PVP) for insulin (INS) delivery was designed. Mechanical testing demonstrated that these MNs possess excellent mechanical strength, capable of withstanding at least 0.11 N per needle without rupture. In vitro drug penetration tests revealed that the MNs consistently released over 75 % of INS within a 6 h. In an animal model, ASMNs@PVP-INS reduced initial blood glucose levels from 22.4 to 5.72 mmol/L, effectively maintaining glucose control for more than 6 h without inducing hypoglycemia. Additionally, agar diffusion assays indicated that INS loading did not compromise the antimicrobial properties of antimicrobial sponge MNs (ASMNs). Skin irritation tests showed that ASMNs@PVP-INS exhibited mild irritation (PII < 0.6), with skin damage fully recovering within 8 h. Safety assessments indicated no significant toxicity to mice, with biochemical markers remaining within normal ranges, thereby confirming their good biocompatibility. In conclusion, ASMNs@PVP-INS hold promise as a novel drug delivery vehicle.

Mechanistic Insights into the Stimulatory Effect of Melanogenesis of 4-Methylcoumarin Derivatives in B16F10 Melanoma Cells.

Vitiligo is a skin condition characterized by the loss of pigment, resulting in white patches on various parts of the body. It occurs when melanocytes, the cells that are responsible for producing skin pigment, are destroyed or stop functioning. This study aimed to investigate the melanogenic potential of various 4-methylcoumarin (4MC) derivatives, including 6-methoxy-4-methylcoumarin (6M-4MC), 7-methoxy-4-methylcoumarin (7M-4MC), 7-amino-4-methylcoumarin (7A-4MC), 6,7-dihydroxy-4-methylcoumarin (6,7DH-4MC), 7,8-dihydroxy-4-methylcoumarin (7,8DH-4MC), and 6,7-dimethoxy-4-methylcoumarin (6,7DM-4MC), in B16F10 melanoma cells. Our findings revealed that, while 4MC, 7A-4MC, 6,7DH-4MC, and 7,8DH-4MC did not exhibit any effect on melanin production, significant stimulation of melanogenesis was observed with 6M-4MC, 7M-4MC, and 6,7DM-4MC, with 6M-4MC demonstrating the most pronounced effect. 6M-4MC significantly stimulated melanin production and tyrosinase activity in a concentration-dependent manner in B16F10 cells. A Western blot analysis revealed that 6M-4MC increased the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Further mechanistic studies showed that 6M-4MC inhibited extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), which led to the upregulation of MITF and TRP proteins and subsequent activation of melanin synthesis. Additionally, 6M-4MC activated GSK3β phosphorylation, reduced β-catenin phosphorylation, and stimulated melanogenesis via the GSK3β/β-catenin pathway. Moreover, a primary skin irritation test was conducted on the upper backs of 32 healthy female volunteers to assess the potential irritation or sensitization from 6M-4MC when applied topically at concentrations of 50 µM and 100 µM. The test results showed no adverse effects on the skin. Collectively, these findings suggest that 6M-4MC may be a promising pigmentation stimulator for use in cosmetics and in the medical treatment of hypopigmentation disorders, particularly in the treatment of skin conditions such as vitiligo.

TRANSETHOSOMES FOR ENHANCED TRANSDERMAL DELIVERY OF METHOTREXATE AGAINST RHEUMATOID ARTHRITIS: FORMULATION, OPTIMISATION AND CHARACTERISATION

Objective: The study aimed to develop and optimise Methotrexate (MTX)-loaded Transethosomal Film-Forming Gel (TE FFG) for transdermal delivery to treat rheumatoid arthritis while alleviating the side associated with oral administration. Methods: The Transethosomes (TE) were prepared using the thin film hydration technique and incorporated into an FFG using chitosan. The Box-Behnken Design method was used to analyse the influence of independent variables such as the concentration of soya lecithin, surfactant, and ethanol on parameters including vesicle size, PDI (Polydispersity Index), zeta potential, and entrapment efficiency. The optimised transethosomal suspension was incorporated into the FFG using 3% chitosan and other excipients. In vitro drug release and ex vivo skin permeation of FFG were performed using Franz diffusion cells. Results: The vesicle size, PDI, zeta potential and entrapment efficiency of the optimised formulation of TE were 110.3 nm, 0.352,-14.4 mV and 49.36%, respectively. The Transmission Electron Microscopy (TEM) image showed that the vesicles were uniform and spherical. The in vitro drug release study was higher for Conventional (CL) FFG) than TE FFG and the drug release mechanism was fitted into the Higuchi model. The permeation was higher for TE FFG, with the steady-state flux being 1.55 times greater than the CL FFG. The skin irritation test on Wistar rats revealed no indication of irritation on the skin. The histopathology examination showed a significant reduction in the inflammatory cells in the treated group. Conclusion: Therefore, the results concluded that the formulated MTX-loaded TE FFG could be a potentially promising substitute for the oral delivery of methotrexate

FORMULATION AND EVALUATION OF LULICONAZOLE NANOEMULGEL USING BOX-BEHNKEN DESIGN APPROACH

Objective: The present study was aimed to develop and assess a Luliconazole-loaded nano emulgel for topical application. Methods: Nanoemulsion of Luliconazole was prepared by ultrasonication method. A pseudo-ternary phase diagram was constructed to determine the ideal ratio of oil and the surfactant/co-surfactant mixture for nanoemulsion preparation. The Box Behnken statistical design was utilized to optimize the nanoemulsion. The optimized batch of nanoemulsion was incorporated into the 1% Carbopol gel as nanoemulgel. It was evaluated for various parameters like globule size, zeta potential, pH, spreadability, viscosity, drug content, drug release, ex vivo permeation study, in vivo animal skin irritation study, and histopathology studies. Results: The optimized formulation showed a globule size of 130.5 nm and entrapment efficiency of 80% and the values were found to be within±5% of predicted values, indicating the suggested statistical model was significant at 95% of confidence interval. The zeta potential of the formulation was found to be-22.1 mV, indicating enhanced stability of the formulation. Transmission Electron Microscopy (TEM) images revealed that the formulation had a smooth surface texture with a mean globule size meeting the nanoscale size range. The drug release study demonstrated a sustained release pattern for the formulation, with a maximum release of 74.93±0.8% over 8 h. The formulated gel exhibited appreciable ex vivo permeability. An in vivo skin irritation test on Wister rats showed no signs of skin irritation from the formulation. The histopathological examination further confirmed that the formulation was dermatologically safe, exhibiting no toxicity or irritation. Conclusion: The results of the present study concluded that Luliconazole-loaded nanoemulgel could be a potential topical drug delivery approach for the management of fungal infections.

Durable and biocompatible low adhesion wound dressing material based on interfacial behaviors for wound management

Wound-dressing adhesion is a problem that has not been effectively addressed in the field of wound care for bleeding or burn wounds. Design of low adhesion wound dressing materials by leveraging interfacial behaviors has been an effective solution to this problem. However, previously reported superhydrophobic low adhesion materials either had durability or biocompatibility issue. To bridge this gap, this study presents a durable and biocompatible superhydrophobic low adhesion wound dressing material, which is designed on a normal gauze substrate with biocompatible components using a hybrid coating strategy. Outstanding low adhesion properties have been verified in vivo with bleeding wound or burn wound, with a peeling force that is only 0.3 %-14.5 % of the conventional non-woven gauze. Prepared low adhesion materials can robustly retain their superhydrophobicity and blood-repelling properties against harsh tests. Moreover, their biocompatibility has been confirmed through a series of tests including cell biocompatibility, hemolysis and skin irritation tests. With these demonstrated merits, the durable and biocompatible low adhesion material developed in this study will provide an effective solution to the wound adhesion problem in the practice of wound management.

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT0-t = 5.96 ± 0.97 h) and the control patch group (MRT0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Cosmeceuticals are the product of cosmetics that are biologically active ingredient that impersonates to medical or drug benefits. But the daily use of synthetic results in many side effects and need of organic lip balms is roaring in the society. In the

Cosmeceuticals are the product of cosmetics that are biologically active ingredient that impersonates to medical or drug benefits. But the daily use of synthetic results in many side effects and need of organic lip balms is roaring in the society. In the present study we, aimed to formulate organic lip balm using natural ingredients. Lip balm has been formulated using Golden shower flower, red cabbage, honey, ghee, beeswax, vitamin E and coconut oil. Various parameters such as stability, melting point, spreadability, pH, were evaluated for the evaluation of lip balm. pH was found to be 6 and melting point was 60°C 65°C for cassia lip balm and red cabbage lip balm respectively. On preforming skin irritation test the formulation was found to be not irritant, and formulation was observed to be stable. Lip balm from above ingredients could be a better option for daily use to a small extend for minor lip issues.

Dermal toxicity studies of 1,2-benzisothiazolin-3-one (CAS number: 2634-33-5) in Sprague-Dawley rats

Biocides are used as preservatives in various household products, and 1,2-benzisothiazolin-3-one (BIT) is one of the popular chemicals. Therefore, BIT is highly likely to be exposed to human skin, necessitating dermal toxicity evaluation. In this study, we aimed to investigate dermal toxicity, eyes and skin irritation, and skin sensitization of BIT. All studies were conducted according to the Organisation for Economic Co-operation and Development testing guidelines. In acute dermal toxicity using rats, no treatment-related responses were observed at the highest dose (2000 mg/kg). A 28-day repeated dermal toxicity study at 1, 4, and 12 mg/kg/day showed transient local skin irritation lesions, including erythema, exfoliation, and crust formation. Based on no systemic effects, the no observed adverse effect level (NOAEL) of BIT of the 28-day repeated dermal toxicity study was determined to be 12 mg/kg/day. Eye and skin irritation tests showed that BIT is a strong irritant and corrosive to the eyes and a mild irritant to the skin. However, BIT showed no skin sensitization reactions in a local lymph node assay. These dermal toxicity studies can provide valuable information for the risk assessment of BIT.

Simvastatin and Captopril Combined Transdermal Delivery System for Controlling Blood Pressure and Fat: Design, Characterization, and In Vivo Pharmacokinetic Evaluation

We developed a sustained-release transdermal drug delivery system (TDDS) containing simvastatin (SIM) and captopril (CAP) to treat hypertension and hyperlipidemia and overcome treatment drawbacks, including significant liver first-pass effects, low bioavailability, and the short half-life of SIM and CAP oral tablets. We used a transdermal diffusion meter to preselect the formula of the SIM-CAP TDDS. Based on in vitro permeation experiments, we optimized the formula of the SIM-CAP TDDS to include 24% SIM, 24% CAP, 34% polyvinyl alcohol (PVA), 16% oleic acid (OA)–azone, and 2% polyacrylic acid resin II. We evaluated the optimized SIM-CAP TDDS formula by its appearance, stability, stickiness, drug content, in vivo pharmacokinetics, and skin irritation tests. The results indicated that the patch had good stability and stickiness. The SIM and CAP contents were 5.02 ± 0.41 mg/cm2 in the 1 cm2 SIM-CAP TDDS. The pharmacokinetic results indicated that the system continuously released SIM and CAP for 24 h and significantly enhanced their bioavailability, with a higher area under the curve. The SIM-CAP TDDS exhibits a sustained-release effect with good characteristics and pharmacokinetics. And it is safe and has no irritating effects on the skin; therefore, it is an ideal formulation.

1-Acetyl-β-Carboline from a Jeju Gotjawal Strain Lentzea sp. JNUCC 0626 and Its Melanogenic Stimulating Activity in B16F10 Melanoma Cells.

The genus Lentzea is a prolific source of bioactive and structurally diverse secondary metabolites. We isolated a novel strain, Lentzea sp. JNUCC 0626, from Hwasun Gotjawal on Jeju Island, Korea. Based on 16S rRNA partial gene sequence analysis, strain JNUCC 0626 is closely related to Lentzea isolaginshaensis NX62 (99.41% similarity), Lentzea pudingi DHS C021 (99.31%), and Lentzea cavernae SYSU K10001 (99.26%). From the fermentation broth of JNUCC 0626, we isolated 1-acetyl-β-carboline, whose structure was established using IR, HR-ESI-MS, and 1D- and 2D-NMR techniques. 1-acetyl-β-carboline was found to activate melanogenesis in mouse B16F10 cells without cytotoxicity at concentrations up to 50 μM. At this concentration, the compound increased melanin content by 27.44% and tyrosinase activity by 240.64% compared to the control, by upregulating key melanogenic enzymes, including tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF), a central regulator of melanogenesis. In addition, 1-acetyl-β-carboline significantly inhibited ERK phosphorylation, reducing it by 20.79% at a concentration of 12.5 μM and by 25.63% at 25 μM. This inhibition supports the hypothesis that 1-acetyl-β-carboline enhances melanin synthesis by upregulating MITF and melanogenic enzymes via the ERK signaling pathway. This study aimed to isolate and identify 1-acetyl-β-carboline from a novel strain of Lentzea sp. JNUCC 0626, discovered in Gotjawal, Jeju Island, and to evaluate its effect on melanin production in B16F10 melanoma cells. Skin irritation tests on 32 subjects confirmed its safety for topical use, and the findings suggest that 1-acetyl-β-carboline, which enhances melanogenesis without cytotoxicity, holds promise as a therapeutic agent for hypopigmentation-related conditions or as a cosmetic ingredient.

Inhibitory Effects of Polyphenols from Equisetum ramosissimum and Moringa peregrina Extracts on Staphylococcus aureus, Collagenase, and Tyrosinase Enzymes: In vitro Studies

Background: Skin problems caused by oxidative stress lead to the activation of collagenase and tyrosinase enzymes, contributing to skin aging, discoloration, and infections. Equisetum ramosissimum and Moringa peregrina were assessed for their potential uses in treating various skin conditions. Objective: The present research aimed to investigate the positive effects of polyphenols in Equisetum ramosissimum and Moringa peregrina extracts as potential cosmetic products for the treatment of different skin conditions. Methods: Total phenolic and flavonoid contents, antioxidants, and anti-collagenase and anti-tyrosinase activities of plant extract mixtures (PEM) at different ratios of (M. peregrina: E. ramosissimum) were determined using standard procedures. Inhibitory effects of PEM against acne-causing Staphylococcus aureus (ATCC 29213) were evaluated using the diameter (cm) of the inhibition zone method. A cream formulation containing PEM was developed and characterized for stability and potential skin irritation in rats using standard procedures. Results: The PEM at a ratio of (2:1) showed the highest total phenolic and flavonoid content (150.15 ± 2.8 mg/g, equivalent to gallic acid, and 41.5 ± 1.2 mg/g, equivalent to quercetin, respectively). Antioxidant activities for PEM (2:1) were also optimal, as determined by the DPPH and ABTS methods (IC50 = 7.06 ± 0.12 µg/mL and 53.29 ± 3.3 µg/mL, respectively). Furthermore, PEM (2:1) exhibited superior inhibitory activities against collagenase and tyrosinase enzymes (IC50 = 32.4 ± 1.19 µg/mL and 8.4 ± 1.19 µg/mL, respectively). Antimicrobial activity of PEM (2:1) tested on S. aureus showed the largest zone of growth inhibition (2.8 cm) at a concentration of 60 mg/mL. Studies on the PEM (2:1) cream formulation revealed that it remained stable under room conditions. Skin irritation tests on rats showed no signs of oedema or erythema after treatment. Conclusion: The PEM with a ratio of (2:1) demonstrated optimal activity as an oxidative stress-neutralizing agent, inhibitor of enzymes responsible for skin aging and hyperpigmentation, and antibacterial agent. The cream formulation containing PEM exhibited physical stability and no detectable risk of skin irritation throughout the research procedures.

Development of levamlodipine long-acting patches based on an ion-pair strategy: Investigation of the mechanism for reducing skin irritation

The aim of this study was to develop a long-acting transdermal patch of levamlodipine (LAM) using an ion-pair strategy to reduce the skin irritation induced by topical application of LAM and explore the mechanism underlying the improvement of skin irritation. The formulation was optimized through porcine in vitro transdermal experiments and rabbit in vivo skin irritation tests. The obtained formulation consisted of poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl) acrylamide) (PENH) as the adhesive matrix, 13.00 % levamlodipine-sorbic acid ion-pair complex (LAM-SA) (w/w), and 10 % isopropyl myristate (IPM) (w/w), with a patch thickness of 70 μm, achieving an erythema index of 188 for rabbit skin and 117–187 for human skin (264 for rabbit skin and 110–260 for human skin in the absence of sorbic acid (SA)). In vivo rabbit and human skin erythema analysis and H&E staining verified that the optimized ion-pair patch effectively reduced skin irritation. Drug distribution experiments in the skin, ATR-FTIR, and molecular simulation were used to characterize the mechanism by which the ion-pair reduced skin irritation. Excessive accumulation of LAM in the epidermis induced secondary structural changes in keratin, resulting in skin barrier damage and inflammatory response. The formation of the LAM-SA ion pair altered physicochemical properties of LAM, reducing drug retention in the epidermis and, thereby, reducing skin irritation. This study demonstrated the potential of the ion-pair strategy to improve the safety of transdermal drug delivery system (TDDS) and provided a means for reducing skin irritation caused by the active pharmaceutical ingredient (API) itself.

In vivo Antifungal Efficacy and Safety of Natural Compounds for Topical Treatment of Cutaneous Candidiasis

In vivo toxicity and antifungal therapeutic evaluation of selected natural compounds for topical applications was analyzed using standard methods. The natural compounds, blue vitriol, brimstone, trona, alum, palm ash and black stone were hygienically selected and purchased at a local market in southeastern Nigeria. The test organisms were isolated from high vaginal swab specimens obtained from cases of cutaneous candidiasis. The isolates were identified based on their morphological, physiological and molecular characteristics. The toxicological screening of the test samples was done using Draize’ skin irritancy test, Murine local lymph node assay (LLNA) and necropsy. The in vivo evaluation of antifungal activity of the solutions was done using eight-week-old albino rats weighing 120g – 150g. The animals were infected with the Candida isolates percutaneously; and treated using various formulations of the natural compounds. The skin sections were carefully observed for histopathological changes, before and after treatment. The total yeast counts of the infected skin tissues were also determined. The isolates include Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Draize’ skin test and Murine local lymph node assay showed no observable skin irritancy reaction (P&gt;0.05). The normal skin architecture of the infected animals was restored after 5 days of treatment with the test samples; while the total yeast count decreased from 108 CFU/mL to 102 CFU/mL. The findings have revealed that natural compounds are effective as well as non-toxic topically, in treatment of cutaneous candidiasis.

Green formulation of Menadione-loaded niosome as a skin-lightening preparation: In vitro/In vivo safety evaluation on Wistar rat

Purpose: In the present research, a green technique (an ultrasonic method) was used to synthesize menadione sodium bisulfite (MSB) niosome (Menasome) which is used to improve dermal delivery and increase anti-melanogenesis activities. Methods: Various cholesterol: surfactant (Chol: Sur) ratios were investigated to optimize the Menasomes. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of MSB in nanoparticle form. Additionally, the optimized formulation was used to investigate ex-vivo skin absorption, in vivo skin irritation, in vitro cell survival, and anti-melanogenesis activity. Results: The results exhibited that increasing cholesterol (Chol) declined the average size of the Menasomes from 653.766±25.171 nm to 298.133±8.823 nm and increased entrapment efficiency 30.237±3.4204% to 83.616±2.550 %. The rat skin permeation study indicated that Menasome gel administered more MSB in dermal layers (439.000±36.190μg/cm2 or 23.827±1.964%) than MSB plain gel (286.200± 22.6μg/cm2 or 15.53±1.227%). In both the in vivo skin irritation test and the in vitro cytotoxicity experiment, the extended-release behavior of the enhanced Menasome demonstrated a minimal side effect profile. Furthermore, optimum Menasome inhibited melanin formation (37.426± 1.644% at 15μM) greater than free MSB (57.383±1.654%) considerably (p &lt;0.05). Furthermore, Menasome 7 prevented L-dopa auto-oxidation in higher levels (95.140±2.439%) than pure MSB solution (83.953±1.629%). Conclusion: According to the study's findings, the prepared Menasome could be employed as a viable nanovehicle for MSB dermal delivery, a promising solution for the management of human hyperpigmentation disorders.

Mosquito repellent propensity of hexane extract of &lt;i&gt;Cymbopogon citratus&lt;/i&gt; Stapf. (Poaceae), lemongrass, cream and emulgel formulations

Malaria is a global threat affecting majorly the African continent with Nigeria having the highest burden of deaths from the disease. Prophylactic measures in addition to curative treatments are strategies used for eradication of malaria. This study aims to develop topical mosquito repellent from lemongrass (Cymbopogon citratus). Lemongrass extract was obtained by Soxhlet extraction using n-hexane, it was formulated as lemongrass extract cream (LGCM) and emugel (LGEM) at 1 and 2% w/w concentrations. Organoleptic properties, spreadability, pH and skin irritation test were evaluated. Percentage mosquito repellency (R) and complete protection time (CPT) assay using the animal (rodent) model were determined and compared with N, N-diethyl-meta-toluamide (DEET). Results showed all the formulations were non-gritty, homogenous, relatively stable upon storage for 30 days at room temperature except forLGCM 1. They were non-irritant to the skin; pH was in range of 5.3 – 8. Spreadability was optimum with LGCM, LGEM 1 and 2% w/w. Mosquito repellency was concentration dependent and ˃ 80% in LGCM 2 and LGEM 2 but emulgels exhibited better repellency. CPT was 4, 5 and 8h for LGCM 2, LGEM 2 and DEET respectively. This study shows that LGEM 2% may be considered as an efficient topical mosquito-repelling formulation.

An ionic liquid nanoparticles for dermal targeted delivery and effective anti-wrinkle treatment

BackgroundAging is a natural process that cannot be stopped but retarded. Hydroxypinacolone retinoate (HPR) is a potent anti-wrinkle agent, but with severe irritancy, low stability, and poor water solubility, making it hard to apply in cosmetics. Ionic liquid (IL), as a solvent, displayed improved transdermal efficiency. The role of nano-encapsulation technology in addressing the disadvantages of efficacy application is significant. ObjectiveUsing a combination of ionic liquids and nano-encapsulation technology to obtain HPR-encapsulated ionic liquid nanoparticles (HPR IL-NPs) is an innovative formulation used as a serum, emulsion, and cream in cosmetics for effective anti-wrinkle. MethodsHPR IL-NPs were prepared using matrine coconut oil ionic liquid as a surfactant and permeation enhancer combined with high-pressure homogenization. ResultsThe average particle size in the obtained HPR IL-NPs was 92.8 nm. Applying the HPR IL-NPs increased the content of active substances in the skin by 3.6-fold compared to a traditional HPR-loaded cream. The chick chorioallantois membrane assay showed an RC50 > 100 %, and repeated skin-irritation tests resulted in a mean value of 0.00 points per animal per day. The HPR IL-NPs showed continuous release for 24 h in vitro in the continuous release test. At the same time, the HPR IL-NPs significantly reduced irritation induced by HPR alone. The number and area of facial wrinkles decreased by 25.09 % and 23.65 %, respectively, after one week of application of liquid cream on volunteers. ConclusionIL NPs can significantly improve transdermal absorption efficiency, reduce irritation, and demonstrate high anti-wrinkle efficiency. Supramolecular liquid cream is a promising product in cosmetics for skin care.

Development of Sensitive In Vitro Protocols for the Biocompatibility Testing of Medical Devices and Pharmaceuticals Intended for Contact with the Eyes: Acute Irritation and Phototoxicity Assessment.

This study introduces a novel in vitro methodology that employs the 3-D reconstructed tissue model, EpiOcular, to assess the irritation and phototoxicity potential of medical devices and drugs in contact with the eye. Our study evaluated diverse test materials, including medical devices, ophthalmological solutions and an experimental drug (cemtirestat), for their potential to cause eye irritation and phototoxicity. The protocols used in this study with the EpiOcular tissue model were akin to those used in the ultra-mildness testing of cosmetic formulations, which is challenging to predict with standard in vivo rabbit tests. To design these protocols, we leveraged experience gained from the validation project on the EpiDerm skin irritation test for medical devices (ISO 10993-23:2021) and the OECD TG 498 method for photo-irritation testing. The predictions were based on the tissue viability and inflammatory response, as determined by IL-1α release. By developing and evaluating these protocols for medical devices, we aimed to expand the applicability domain of the tests referred to in ISO 10993-23. This will contribute to the standardisation and cost-effective safety evaluation of ophthalmic products, while reducing reliance on animal testing in this field. The findings obtained from the EpiOcular model in the photo-irritation test could support its implementation in the testing strategies outlined in OECD TG 498.

Reliability and relevance of the ES®-RHE model for in vitro skin irritation test application

IntroductionIn vitro methods have been widely used to assess adverse effects. Reconstructed Human Epidermis (RHE) poses as a fascinating test system employed to assess the dermal irritation hazard potential of chemicals. Although several RHE models are reported in the OECD Test Guideline No. 439, the OECD Document No. 220 encourages the scientific community to develop and validate new RHE test systems due to its relevance for socio-economic advancement. MethodsFollowing the criteria documented in the OECD No. 220, a blind study for skin irritation (OECD 439) was conducted employing the Minimum List of Reference Chemicals for Determination of Reproducibility and Predictive Capacity using ES®-RHE. Structural and functional characteristics were assessed alongside the prediction model. ResultsThe model has shown reproducibility of optical density and barrier function, similarly to internationally validated methods. Furthermore, it shows the cell layers' development and differentiation ability due to Cytokeratin14, Cytokeratin10, and filaggrin expression. The prediction model resulted in sensitivity, specificity and accuracy rates of 100, 70, and 77 %, respectively. ConclusionsThe ES®-RHE demonstrated reliability and relevance, with similar structural and functional characteristics comparable to internationally validated models, in addition to the accepted predictive capacity according to OECD required minimum criteria, thus confirming the suitability of the national ES®-RHE in the hazard prediction of dermal irritation based on OECD Test Guideline No. 439.