Dermal Application Research Articles

Benzisothiazolinone: Pharmacokinetics, Tissue Distribution, and Mass Balance Studies in Rats.

Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration. BIT levels were determined in rat plasma and tissues after oral inhalation and dermal application. Although the digestive system rapidly and completely absorbed orally administered BIT, it underwent severe first-pass effects that prevented high exposure. In an oral dose escalation study (5-50 mg/kg), nonlinear pharmacokinetic properties showed that Cmax and the area under the curve (AUC) increased more than dose proportionality. In the inhalation study, the lungs of rats exposed to BIT aerosols had higher BIT concentrations than the plasma. Additionally, the pharmacokinetic profile of BIT after the dermal application was different; continuous skin absorption without the first-pass effect led to a 2.13-fold increase in bioavailability compared with oral exposure to BIT. The [14C]-BIT mass balance study revealed that BIT was extensively metabolized and excreted in the urine. These results can be used in risk assessments to investigate the relationship between BIT exposure and hazardous potential.

Assessment of dermal toxicity of mustard oil based formulation of Nerium indicum Mill.

Nerium indicum Mill. with red flowers belong to family Apocynaceae is considered as botanical source of Rakta Karavira drug of Upavisha (semi-poisonous) category of Ayurvedic Pharmacopeia of India. Till date Rakta Karavira Taila (mustard oil based formulation of root bark of Rakta Karavira) has not been evaluated pharmacologically. In present study, acute and repeated dose 28 day dermal toxicity studies of Rakta Karavira Taila was carried out in Charles foster albino rats. Acute dermal toxicity study was assessed at a single dermal application of drug at limit dose of 2000 mg/kg body weight of rats and observed for fourteen consecutive days. The repeated dose 28-day dermal toxicity study was assessed on repeated dermal applications at limit dose of 1000 mg/kg body weight of rats for 28 days consecutive days as per OECD guideline. The test medication was applied equally over a region covering rats body surface area of about 10%. Effects on body weight, haematological, ponderal changes, biochemical, and histological studies were used to evaluate the toxicity of the Rakta Karavira Taila. No mortality and toxicity were observed on single dermal application at limit dose level of 2000 mg/kg in acute dermal toxicity study. On repeated dermal applications of Rakta Karavira Taila at limit dose of 1000 mg/kg, showed statistically significant decrease in weight of testes, increase in WBC and platelet count while rest of hematological and biochemical parameters are not affected in comparison to control group. Histopathological study showed inflammation and fatty degenerative changes in liver and kidney, degenerative changes in seminiferous tubules and decrease in spermatogenesis in drug administered group. Medicated oil prepared out of root bark of Nerium indicum with red flower with mustard oil has potential to produce adverse effect particularly on male reproductive system therefore, should not be used for longer duration at higher dose level.

Evaluation of the cellular effects of silica particles used for dermal application

ABSTRACT The cellular effects of 5 types of spherical amorphous silica particles whose particle size were 4.2–12.8 μm for cosmetic use and two types of crystalline silica whose particle size were 2.4 and 7.1 μm particles for industrial use were examined. These silica particles were applied to HaCaT human keratinocytes for 24 hr. Crystalline silica enhanced IL-8 and IL-6 expression and caused cell membrane damage. Crystalline silica also enhanced HO-1 gene expression; however, the level of intracellular ROS did not change. Compared with crystalline silica, the cellular effects of the spherical silica employed in this study were minor. Cellular uptake of particles was observed for all of silica particle types. Cellular uptake of crystalline silica was observed 1 hr after exposure, and internalized silica particles were present in the cytoplasm. When HaCaT cells were exposed to crystalline silica for 1 hr and incubated for 23 hr in culture medium without silica particles, IL-8 expression was still detected. In addition, silica particles exerted negligible effects using a 3D skin tissue model. Thus, the following conclusions may be drawn. (1) cellular effects exerted by spherical silica are less compared to crystalline silica. (2) phagocytosis of particles is an important first step in the cellular effects of silica particles. (3) spherical silica particles might exert little, if any, effect on healthy skin attributed to no apparent cellular uptake.

Intrinsic Permeation and Anti-Inflammatory Evaluation of Curcumin, Bisdemethoxycurcumin and Bisdemethylcurcumin by a Validated HPLC-UV Method

Curcumin shows anti-inflammatory activity, and it has been widely investigated for neurodegenerative diseases, adjuvant treatment in AIDS and antitumor activity against different tumors, among other activities. The goal of this work was to evaluate the capacity of curcumin and its derivatives (bisdemethoxycurcumin and bisdemethylcurcumin) in preventing the irritant effects of topically applied xylol and to assess the intrinsic capacity of curcuminoids in permeating human skin by ex vivo permeation tests. Its secondary goal was to validate an HPLC method to simultaneously determine the curcuminoids in the samples from the ex vivo permeation studies and drug extraction from the skin. Curcuminoid quantification was performed using an RP-C18 column, at isocratic conditions of elution and a detection wavelength of 265 nm. The method was specific with a suitable peak resolution, as well as linear, precise, and accurate in the range of 0.195-3.125 μg/mL for the three curcuminoids. Bisdemethylcurcumin showed the greatest permeation through the human skin, and it was the curcuminoid that was most retained within the human skin. The anti-inflammatory activity of the curcuminoids was evaluated in vivo using a xylol-induced inflammation model in rats. Histological studies were performed to observe any changes in morphology at the microscopic level, and these three curcuminoids were found to be respectful within the skin structure. These results show that these three curcuminoids are suitable for anti-inflammatory formulations for dermal applications, and they can be properly quantified using HPLC-UV.

Comparative assessment of different methods of studying skin toxicity of powder for wounds

The article provides data on the comparative assessment of the study of acute and subacute dermal toxicity of powder for wounds made based on iodoform by various methods. The research was conducted using the classic method and according to the methodology of the Organization for Economic Cooperation and Development (OECD No. 410). When studying acute skin toxicity using the traditional method, it was established that the drug under study belongs to the IV toxicity class (low-toxic substances) and, when determined by the way according to the UGS (GHS) – to category 5. During long-term dermal application of powder for wounds, no significant changes in hemoglobin concentration, hematocrit value, the average concentration of hemoglobin in erythrocytes (MCHC), the average volume of erythrocytes (MCV), the average content of hemoglobin in erythrocytes (MCH) and several platelets were established by the classical method. In addition, a slight increase in creatinine, urea, and the activity of ALT and AST was established against a slight decrease in the total protein content. When studying the acute toxicity of powder for wounds following the OECD method No. 410, it was confirmed that long-term dermal application of the investigated agent caused a slight increase in the weight coefficients of the liver, heart, and spleen and a probable increase in the weight coefficients of the kidneys against the background of a decrease in the body weight of animals. Also, in animals of all experimental groups, the number of erythrocytes increased by 0.6 %, 5.1 %, and 10.5 % (Р < 0.05), respectively, and the number of leukocytes decreased by 15.9 % (Р < 0.05), 21.8 % (Р < 0.05), 23.4 % (Р < 0.05), mean erythrocyte volume (MCV) by 2.4 %, 4.2 %, 9.2 % (Р < 0,05). When determining the biochemical indicators of blood serum, it was established that using the research product for 28 days caused a slight decrease in the total protein content in animals of the I, II, and III research groups. In addition, the animals of all experimental groups showed an increase in the level of creatinine, respectively, by – 10.6 % (Р < 0.05), 13.3 % (Р < 0.05), 15.4 % (Р < 0.05), urea at – 3.3 %, 7.3 % (Р < 0.05), 12.6 % (Р < 0.05).

Skin penetration of active folate salts and their effects on wound healing in vitro: new approaches for dermal folate application

# Objectives The skin has a high demand for folates because of its constant renewal and growth. Folates play an important role in the metabolism of healthy skin and in the regeneration of irritated or injured skin. The high proliferation rate supports wound healing in chronic and degenerative skin diseases. In contrast to systemic folate administration, there is little known on skin penetration of folates after topical application. Therefore, skin penetration with L-formyltetrahydrofolate di-arginine salt (L-FTHF-di-arginine), L-formyltetrahydrofolate calcium gluconate mixture (L-FTHF-Ca) and L-methyltetrahydrofolate dicholine salt (L-MTHF-dicholine) was studied. # Methods We investigated the epidermal penetration of 2.5% aqueous solution of L-FTHF di-arginine, L-FTHF Ca and L-MTHF dicholine using *in vitro* reconstructed epidermal skin models. These multi-layered epidermis models closely emulate the barrier of human skin. Aqueous solutions of - L-FTHF di-arginine, L-FTHF Ca and L-MTHF dicholine were applied topically to the keratinized layer. The folate concentration below the multi-layer was analyzed after 24 hours by high-performance liquid chromatography (HPLC)-analysis to detect penetration. In order to assess an effect on wound healing *in vitro*, the selected folates were tested in a keratinocyte scratch assay. # Results Analysis of the examined folates in the cell culture medium located opposite of the application site showed their penetration through the reconstructed epidermal model. In epidermal models to which L-FTHF di-arginine was added, L-MTHF dicholine was detected on the opposite site. L-FTHF salts were partially converted to L-MTHF. Improved wound healing was shown in keratinocyte scratch assay when the selected folates were added to the medium. # Conclusion The *in vitro* experiments on an epidermal skin model have revealed the following new findings: a) the different reduced folates investigated (L-FTHF di-arginine, L-FTHF Ca and L-MTHF dicholine) penetrate well into and through the skin, in contrast to folic acid, which is commonly used; b) they neither disturb the viability of skin cells nor their barrier function, but even improve it; c) the proliferation and migration of epidermal cells, which is important for wound healing, is promoted; d) epidermal cells are able to convert L-FTHF locally into L-MTHF, i.e., to the dominant biologically active form in the circulation. This creates important prerequisites for a future topical application of folates for the treatment of certain skin diseases and the prophylaxis of skin aging processes.

Preparation and Investigation of Thermally Annealed Zein-Propolis Electrospun Nanofibers for Biomedical Applications.

Zein, a corn-derived protein, has a variety of applications ranging from drug delivery to tissue engineering and wound healing. This work aims to develop a biocompatible scaffold for dermal applications based on thermally annealed electrospun propolis-loaded zein nanofibers. Pristine fibers' biocompatibility is determined invitro. Next, propolis from Melipona quadrifasciata is added to the fibers at different concentrations (5% to 25%), and the scaffolds are studied. The physicochemical properties of zein/propolis precursor dispersions are evaluated and the results are correlated to the fibers' properties. Due to zein's and propolis' very favorable interactions, which are responsible for the increase in the dispersions surface tension, nanometric size ribbon-like fibers ranging from 420 to 575nm are obtained. The fiber's hydrophobicity is not dependent on propolis concentration and increases with the annealing procedure. Propolis inhibitory concentration (IC50 ) is determined as 61.78µgmL-1 . When loaded into fibers, propolis is gradually delivered to cells as Balb/3T3 fibroblasts and are able to adhere, grow, and interact with pristine and propolis-loaded fibers, and cytotoxicity is not observed. Therefore, the zein-propolis nanofibers are considered biocompatible and safe. The results are promising and provide prospects for the development of wound-healing nanofiber patches-one of propolis' main applications.

Analytical Method Development of Benzisothiazolinone, a Biocide, Using LC-MS/MS and a Pharmacokinetic Application in Rat Biological Matrices.

Benzisothiazolinone (BIT), a biocide widely used as a preservative in household cleaning and personal care products, is cytotoxic to lung cells and a known skin allergen in humans, which highlights the importance of assessing its toxicity and pharmacokinetics. In this study, a simple, sensitive, and accurate LC-MS/MS method for the quantification of BIT in rat plasma, urine, or tissue homogenates (50 μL) using phenacetin as an internal standard was developed and validated. Samples were extracted with ethyl acetate and separated using a Kinetex phenyl-hexyl column (100 × 2.1 mm, 2.6 μm) with isocratic 0.1% formic acid in methanol and distilled water over a run time of 6 min. Positive electrospray ionization with multiple reaction monitoring transitions of m/z 152.2 > 134.1 for BIT and 180.2 > 110.1 for phenacetin was used for quantification. This assay achieved good linearity in the calibration ranges of 2-2000 ng/mL (plasma and urine) and 10-1000 ng/mL (tissue homogenates), with r ≥ 0.9929. All validation parameters met the acceptance criteria. BIT pharmacokinetics was evaluated via an intravenous and dermal application. This is the first study that evaluated BIT pharmacokinetics in rats, providing insights into the relationship between BIT exposure and toxicity and a basis for future risk assessment studies in humans.

Antioxidative and Antimicrobial Evaluation of Bark Extracts from Common European Trees in Light of Dermal Applications.

Plant species have developed effective defense strategies for colonizing diverse habitats and protecting themselves from numerous attacks from a wide range of organisms, including insects, vertebrates, fungi, and bacteria. The bark of trees in particular constitutes a number of components that protect against unwanted intruders. This review focuses on the antioxidative, dermal immunomodulatory, and antimicrobial properties of bark extracts from European common temperate trees in light of various skin pathogens, wound healing, and the maintenance of skin health. The sustainability aspect, achieved by utilizing the bark, which is considered a byproduct in the forest industry, is addressed, as are various extraction methods applied to retrieve extracts from bark.

Dermal exposure and hair dye: Assessing potential bladder cancer risk from permanent hair dye

Hair dye products include a range of chemicals, depending on the type and color. A common primary intermediate compound used to achieve the permanent effect of hair dye is para-phenylenediamine (PPD). 4-aminobiphenyl (4-ABP) has reportedly been found as a trace contaminant (presumably from the para-phenylenediamine [PPD] ingredient) in consumer permanent hair dye. While several regulatory agencies have designated 4-ABP as a human bladder carcinogen based on evidence in humans and experimental animals, only the Office of Environmental Health Hazard Assessment (OEHHA) have established a cancer risk value for 4-ABP of 0.03 μg/day based on liver tumors developed in mice. A hypothetical dermal risk assessment was performed to estimate the bladder cancer risk associated with exposure to 4-ABP from personal use of permanent hair dye potentially containing incidental 4-ABP. Previously published laboratory analyses characterizing 4-ABP concentrations in consumer hair dyes indicate the concentrations can range from below the limit of detection to 8120 ppb. Precautionary estimates of human scalp surface area, maximum skin adherence, hair dye retention factor, and percent dermal absorption were used to estimate the daily systemic exposure doses (SEDs) from dermal application of hair dye. The estimated SEDs ranged from 0.05 to 3000 pg/day. A margin of safety (MOS) was calculated as the ratio of the NSRL to the SED and ranged from 10 to 570,000. The results of this study suggest that there is no indication of increased risk of bladder cancer in humans from exposure to 4-ABP in consumer hair dye, especially as it is extremely unlikely that a consumer would use permanent hair dye on a daily basis (as this assessment models).

Investigation and multiscale modeling of PVA/SA coated poly lactic acid scaffold containing curcumin loaded layered double hydroxide nanohybrids.

Applying hydrophilic coatings on polymeric nanofibers combined with layered double hydroxide (LDH) not only enhances the efficiency of drug delivery systems but also increases cell adhesion. This work aimed to prepare poly(vinyl alcohol)/sodium alginate (PVA/SA) (2/1)-coated poly(lactic acid) (PLA) nanofibers containing curcumin-loaded layered double hydroxide (LDH) and to investigate their drug release and mechanical properties and their biocompatibility. The optimum PLA nanofibrous sample was considered to be that based on 3 wt% of curcumin-loaded LDH (PLA-3%LDH) with a drug encapsulation efficiency of ∼18% in which a minimum average nanofiber diameter of ∼476 nm along with a high tensile strength of 3.00 MPa were obtained. In the next step, a PVA/SA (2/1) layer was coated on the PLA-3%LDH; as a result, the hydrophilicity of the sample was improved and the elongation at break was decreased remarkably. In this regard the cell viability reached 80% for the coated PLA. Moreover, the formation of a layer of (PVA/SA) on the PLA nanofibers lowered the burst release and resulted in a more sustained drug release, which is a vital feature in dermal applications. A multiscale modeling method was applied for simulation of the mechanical properties of the composite scaffold and the results showed that this method can predict the data with 83% accuracy. The results of this study indicate that the formation of a layer of PVA/SA (2/1) has a significant effect on hydrophilicity and consequently improves cell adhesion and proliferation.

THE SUB-ACUTE TOXICITY OF THE DISINFECTIOUS PREPARATION "IODOPOVIDONE"

The results of a preclinical study of the subacute toxicity of the disinfectant "Iodopovidone" are presented. The purpose of the experiment reflected in the article was to continue a series of preclinical studies of the disinfectant Iodopovidone on laboratory animals by examining subacute toxicity, to confirm good animal tolerance and the drug belongs to the 4th toxicity class – low-toxic substances. The experiment was carried out on laboratory white rats, which were kept in the vivarium of the Faculty of Veterinary Medicine of the National University of Life and Environmental Sciences of Ukraine in compliance with the requirements of the European Convention for the Protection of Vertebrate Animals used for scientific experiments or for other scientific purposes and the Law of Ukraine "On the Protection of Animals". The subacute toxicity of the disinfectant "Iodopovidone" was studied using dermal application. The effect of the drug was evaluated by analyzing the change in biochemical parameters of blood serum and hematological parameters of the blood of laboratory animals in dynamics after 6, 24 and 48 hours. The results of determining the parameters of subacute toxicity when applied to the skin indicate the absence of an irritating effect of the drug on the skin. Under the influence of the drug on the organism of animals for six hours, a slight fluctuation in hematological and biochemical blood parameters was revealed, which approached those of the control group of animals within 48 hours, except for the level of glucose, but this did not affect the general condition of the animals. The use of the drug at a dose of 2900 mg/kg of body weight does not cause the death of animals, which confirms the low toxicity of the drug and belonging to the 4th class of toxicity according to the current sanitary and hygienic standards, which is promising for use in poultry farming and requires further studies of chronic toxicity and toxicity in inhalation use.

Hydrogels for dermal and transdermal drug delivery.

A painless and non-invasive method to deliver drugs using dermal and transdermal administration routes has been expanding for more than 30 years as it reduces the risk of drug overdoses that can be associated with oral administrations or injections. To understand the particularities of this drug delivery pathway, we will present a rapid review of the skin, including its structure and the parameters that influence drug diffusion into it, and then discuss the strategies that improve dermal drug delivery. Of the multitude of existing systems used for topical dermal and transdermal applications, this review will focus on the breakthroughs in drug delivery systems made of hydrogels. Specifically, we will firstly present the use of hydrogels as innovative drug delivery vehicles to carry the active ingredient and penetrate the skin barrier. We will discuss the structure of hydrogels and the physicochemical parameters to master for improving drug delivery, as well as the drug encapsulation and release processes from hydrogels. In the last part, we will review the use of hydrogels as pharmaceutical forms associated with other vehicles - as emulsions, lipid nanoparticles, vesicles, capsules and polymeric or inorganic nanoparticles - suitable for skin penetration enhancement and drug protection, as well as side effects that may limit their use.

Ethical Concerns in Dermatology and Cosmetic Applications

Our aim in this article is to consider ethical concerns and sensitivities in Dermatology and Cosmetic applications. It is appropriate for dermatologists to make cosmetic applications and use artificial intelligence aid as experts who know the structure and diseases of the skin best. The practice of cosmetology by physicians other than dermatologists creates ethical problems. Women are especially more interested in dermatology. Body dysmorphic disorders are more common in women. When dermatologists evaluate the cosmetic dermatology patient and create a treatment plan, if there are unrealistic expectations, the patient should be guided correctly by considering the patient's wishes. Social media applications, which have attracted attention in recent years, have caused an increase in body dysmorphic disorders in individuals. Cosmetology is a division that can never be separated from dermatology. Patients frequently apply to cosmetic dermatology because of hyperpigmentation problems, aging problems, hair problems, toxin applications, dermal filler procedures, chemical peels, and mesotherapy, and ablative laser procedures. Burns resulting from laser epilation applications performed in aesthetic centers, complications such as tissue necrosis caused by dermal filler procedures performed by non-physicians, cosmetic problems, soft tissue infections, and allergic reactions resulting from applications such as mesotherapy and platelet-rich plasma are diseases frequently seen in dermatology outpatient clinics. Another important issue is the materials used in platelet-rich plasma, mesotherapy, toxin application, and dermal filler applications must be in the Class 3 Medical device category. Patients who apply to clinics for treatment should be made aware of this issue and patients should be protected from the complications that these medications may cause. Physicians should not use products that do not have class 3 certificates in cosmetic dermatology to keep the cost of the product low, especially when choosing materials. In medicine, there is always an aesthetic concern beyond technical or even scientific concerns. We think that it is necessary to express and elaborate on the concerns arising from the ethical issues that are experienced or may be experienced in dermatology practices. Physicians always try to take the patient's psychological and pathological problems into consideration. However, ethical concerns should not be forgotten when treating the field of aesthetics.

A Case of Laying Hens Mycosis Caused by Fusarium proliferatum.

In this article, we present the first case report of a chicken mycosis caused by F. proliferatum occurred on a private farm in the Russian Federation. Lesions on the skin of the legs and scallops were reported. The object of this study was samples of feed and pathological material from sick hens-layers. Mycological analysis included determination of the total number of fungi (TNF) and identification and determination of the toxicity and pathogenicity of the isolates. The identification of the isolate was carried out taking into account direct microscopy, morphological features, and the method of molecular genetic analysis. Microscopic fungi of the genus Penicillium and Rhizopus were isolated by mycological analysis of the feed. The test feed was nontoxic. Mycological examination of pathological material (scrapings from the combs and affected legs) identified an isolate of Fusarium proliferatum, which showed toxicity on biological objects (protozoa, rabbits) and pathogenicity (white mice). Dermal application of F. proliferatum suspension was accompanied by reddening of the rabbit skin. Intraperitoneal injection of fungal spores caused mycosis in white mice. Polymerase chain reaction (PCR) made it possible to identify this type of microscopic fungus (F. proliferatum) with high accuracy in the samples under study. The research results allow us to consider F. proliferatum as a cause of poultry disease against the background of predisposing factors in the form of desquamation of the stratum corneum of the skin against the background of immunosuppression and metabolic disorders caused by an imbalance in the diet.

Subacute exposure to bisphenol F diglycidyl-ether induces chronic dermatitis characterized by psoriasis-like skin inflammation in mice.

Bisphenol F diglycidyl ether (BFDGE) is widely used in the synthesis process of plastic products. While exposure to bisphenol A diglycidyl ether (BADGE), which has a similar structure to BFDGE and which is used for the same purpose, has been reported to cause health risks, there is still little information on BFDGE. Because it is estimated that the industrial workers are exposed to large amounts of BFDGE, the health risks associated with BFDGE exposure need to be clarified. We investigated the toxicity of cutaneous exposure to BFDGE using an in vitro evaluation system and a mouse exposure model. The tumorigenic potential of BFDGE was confirmed by the Bhas 42 cell transformation assay, which showed that BFDGE has both promoter and initiator activity, in vitro. A single dermal application of BFDGE was associated with minor contact hypersensitivity symptoms. In contrast, repeated dermal exposure to BFDGE for 2 weeks induced persistent acute inflammation with features similar to inflammation in human psoriasis. This is the first report evaluating the toxicity of BFDGE in animals, and we showed that BFDGE carries a health risk of inducing skin dermatitis similar to that in human psoriasis in an exposure period-dependent manner.

Topical glucocorticoid application causing iatrogenic Cushing’s syndrome followed by secondary adrenal insufficiency in infants: two case reports

BackgroundIatrogenic Cushing’s syndrome induced by oral and parenteral glucocorticoid administration is a well-known complication. Immediate withdrawal from exogenous steroids can lead to life-threatening adrenal insufficiency. However, Cushing’s syndrome caused by topical treatment with glucocorticoids, such as dexamethasone eye drops or dermal application, is rarely recognized. Young infants in particular are at high risk of suffering from iatrogenic Cushing’s syndrome when treated with highly potent topical glucocorticoids.Case presentationWe present a 6-month-old Syrian boy with cushingoid face after dermal clobetasol cream treatment and a 2-year-old Iranian girl with severe growth retardation after application of dexamethasone eye drops. Both families have a migration background and language barriers. In both cases no endogenous cortisol secretion was initially detected in serum and in 24-hour collected urine. After dose reduction of glucocorticoids, severity of symptoms was reversible and serum cortisol was detectable.Discussion and conclusionYoung infants are at high risk of developing Cushing’s syndrome from topically applied highly potent glucocorticoids. Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter. Monitoring of height and weight as well as regular pediatric follow-ups should be scheduled. Physicians should be aware of potential adrenal insufficiency following withdrawal from long-term topical glucocorticoid treatment, and hydrocortisone treatment should be considered.

Antioxidant, dermal and acute toxicological effects of Eucalyptus camaldulensis (Dehn-Blakely) essential oil on male Wistar rats

During the era of the COVID-19 lockdown, many Nigerians resorted to home remedies like herbal mixtures for therapy because they could not have access to orthodox medicine. Eucalyptus camaldulensis (E. camaldulensis) essential oil was one of such remedies as many believed it had the potential to treat colds, flu, sore throats, bronchitis and even prevent SARS-CoV-2 infection.
 The objective of the study is to check the antioxidant, dermal and acute toxicological effects of the E. camaldulensis essential oil. Rats were grouped into 8 of 5 each. Normal and corn oil (2ml/kg body weight) control groups. E. camaldulensis essential oil from Jos, Niger, Nasarawa, Kogi, Kwara, and Benue zones were given at 2ml/kg body weight for 14 days as well as applied on the shaved skin of the rats. No mortality was recorded in the sub-acute toxicity study at low and high doses (10mg/kg and 5000mg/kg). The levels of AST, ALT, TNF-α and IL-6 did not significantly differ from normal control rats. Lungs Investigation recorded a significant increase in the TNF-α. Antioxidant enzyme assays showed a significant increase in catalase, superoxide dismutase and glutathione-s-transferase. Histological examination showed focal inflammation with moderate cytoplasmic clearing in the liver and focal mild epidermal sclerosis of the skin. Dermal application of the oil shows no significant toxic effect except some mild inflammation (skin irritation). Oral administrations were relatively safe with mild adverse effect observed in the lung inflammatory markers.

Mucogingival surgery with SureDerm application for gingival recession treatment in periodontics clinic University of Airlangga in 2022

Background: Gingival recession has become a serious problem since it has a high prevalence among the 88% population of the world. Various mucogingival therapy becomes treatment of choice for gingival recession, such as sub ephitelial connective tissue graft, coronally positioned flap, an acellular dermal matrix application. SureDerm as an acellular dermal matrix can be used for gingival recession treatment. Case: A 22-year old male patient came to Periodontics Specialist Clinic in Dental Hospital Universitas Airlangga with the chief complaint of dental hypersensitivity on the left mandibular posterior molar teeth when stimulates with heat or cold sensation. Methods and Treatment Results: Coronally Advanced Flap with Tunnelling technique was conducted using a scalpel and, TKN (Tunnelling Knife), with the additional use of acellular dermal matrix (Surederm). The success of this treatment depends on the technique and procedure used in this treatment, and is measured by the absence of further complaints and the correction of gingival recession. Conclusion: Coronally Advanced Flap management is related with pre-evaluation before surgical procedure and the basic of surgical procedure that is being used.

Cyclodextrin-based nanogel of flurbiprofen for dermal application: In vitro studies and in vivo skin irritation evaluation

The aim of this study was to develop and characterize flurbiprofen (FB)-loaded cyclodextrin (CD) based nanogel formulations for dermal application. Nanogels were produced via emulsification solvent evaporation and then incorporated into a hydroxypropyl methyl cellulose (HPMC) gel. The visual examination, pH, viscosity, dynamic rheological measurements and drug content analysis of nanogels were assessed. In vitro and ex vivo permeation, stability, and skin irritation were performed. pH of the FB-loaded nanogel and the nanogels in HPMC were 10.6 ± 0.1 and 7.5 ± 0.1 (neutral) respectively. The highest and lowest viscosities were observed in FB-loaded nanogels and in FB-free nanogels in HPMC, respectively. The tangent δ and storage modulus values of FB-loaded nanogel in HPMC were higher than those of FB-loaded nanogel. FB from nanogels in HPMC was 100% by 48 h. The final nanogel formulation was physically and chemically stable over 12 months. Skin irritation test showed no skin irritation or cellular infiltration on the histological level. In vitro and ex vivo permeation showed that the nanogels could be effective and stable formulations, especially in the dermal application of a hydrophobic molecule.