Topical menthol, a pharmacological cold mimic, induces cold sensitivity, adaptive thermogenesis and brown adipose tissue activation in mice.

AIM: Brown adipose tissue (BAT) thermogenesis has profound energy-expanding potential, which makes it an attractive target tissue to combat ever-increasing obesity and its other associated metabolic complications. Although it is fairly accepted that cold is a potent inducer of BAT activation and function, there are limited studies on the mechanisms of pharmacological cold-mimicking agents, such as the TRPM8 agonist, menthol, on BAT thermogenesis and activation. METHODS: Herein, we sought to determine the effect of topical application of menthol (10% w/v [4 g/kg] cream formulation/day for 15 days) on temperature sensitivity behaviour (thermal gradient assay, nesting behaviour), adaptive thermogenesis (infrared thermography, core body temperature), BAT sympathetic innervation (tyrosine hydroxylase immunohistochemistry) and activation (18F-FDG PET-CT analysis, Uncoupling Protein 1 immunohistochemistry and BAT gene expression), whole-body energy expenditure (indirect calorimetry) and other metabolic variables in male C57BL/6N mice. RESULTS: We show that male C57BL/6N mice: (a) develop a warm-seeking and cold-avoiding thermal preference phenotype; (b) display increased locomotor activity and adaptive thermogenesis; (c) show augmented sympathetic innervation in BAT and its activation; (d) exhibit enhanced gluconeogenic capacity (increased glucose excursion in response to pyruvate) and insulin sensitivity; and (e) show enhanced whole-body energy expenditure and induced lipid-utilizing phenotype after topical menthol application. CONCLUSIONS: Taken together, our findings highlight that pharmacological cold mimicking using topical menthol application presents a potential therapeutic strategy to counter weight gain and related complications.

Examining the association between untreated caries in children and parent fluoride treatment refusal.

BACKGROUND: In this case-control study, the authors examined the relationship between untreated caries in children and parent fluoride treatment refusal. The authors hypothesized that parents of children with a history of untreated caries would be less likely to refuse topical fluoride for their children than parents of children with no history of untreated caries. METHODS: The study included children (≤ 18 years old) who were patients at a university dental clinic from January 2016 through June 2020. Children whose parents refused fluoride treatment were age-matched with children whose parents did not refuse fluoride treatment (n = 356). The outcome variable was parent topical fluoride refusal for their children (no, yes). The predictor variable was a history of untreated caries (no, yes). Confounding variable-adjusted modified Poisson regression models were used to estimate the prevalence ratio of parent fluoride refusal by means of children's untreated caries status. RESULTS: Approximately 46.3% of children had a history of untreated caries. The prevalence of parent fluoride refusal for children with a history of untreated caries was significantly lower than that for children with no history of untreated caries (adjusted prevalence ratio, 0.79; 95% CI, 0.64 to 0.98; P = .03). CONCLUSIONS: Parents of children with a history of caries are less likely to refuse topical fluoride treatment, which suggests that untreated caries may motivate parents to accept preventive dental treatments like fluoride. PRACTICAL IMPLICATIONS: Dental care professionals should assess caries risk and communicate a child's caries risk before making a recommendation regarding topical fluoride treatment.

[Translated article] Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥85% agreement in 22 recommendations and≥70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

Topical Semisolid Drug Product Critical Quality Attributes with Relevance to Cutaneous Bioavailability and Pharmacokinetics: Part I-Bioequivalence of Acyclovir Topical Creams.

PURPOSE: To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT). METHODS: Product attributes representing the physicochemical and structural (Q3) arrangement of matter, such as attributes of particles and globules, were assessed for a set of test acyclovir creams (Aciclostad® and Acyclovir 1A Pharma) and compared to a set of reference acyclovir creams (Zovirax® US, Zovirax® UK and Zovirax® Australia). IVPT studies were performed with all these creams using heat-separated human epidermis, evaluated with both, static Franz-type diffusion cells and a flow through diffusion cell system. RESULTS: A toolkit developed to characterize quality and performance attributes of these acyclovir topical cream products identified certain differences in the Q3 attributes and the cutaneous PK of acyclovir between the test and reference sets of products. The cutaneous BA of acyclovir from the set of reference creams was substantially higher than from the set of test creams. CONCLUSIONS: This research elucidates how differences in the composition or manufacturing of product formulations can alter Q3 attributes that modulate myriad aspects of topical product performance. The results demonstrate the importance of understanding the Q3 attributes of topical semisolid drug products, and of developing appropriate product characterization tests. The toolkit developed here can be utilized to guide topical product development, and to mitigate the risk of differences in product performance, thereby supporting a demonstration of bioequivalence (BE) for prospective topical generic products and reducing the reliance on comparative clinical endpoint BE studies.

Insight into Olfactory Learning, Memory, and Mortality of Apis mellifera jemenitica after Exposure to Acetamiprid Insecticide.

The honey bee, a significant crop pollinator, encounters pesticides through various routes of exposure during foraging and flower visitation. Considering the potential threat of pesticide poisoning, the indigenous Saudi bee Apis mellifera jemenitica is susceptible to the risks associated with acetamiprid, a neonicotinoid insecticide. This study investigates the acetamiprid-induced effects on the survival, olfactory learning, and memory formation of A. m. jemenitica through two exposure routes: topical application and oral ingestion. Field-realistic and serially diluted concentrations (100, 50, 25, and 10 ppm) of acetamiprid led to notable mortality at 4, 12, 24, and 48 h after treatment, with peak mortality observed at 24 h and 48 h for both exposure routes. Bee mortality was concentration-dependent, increasing with the rising concentration of acetamiprid at the tested time intervals. Food consumption following oral exposure exhibited a concentration-dependent pattern, steadily decreasing with increasing concentrations of acetamiprid. Oral exposure resulted in a substantially higher cumulative mortality (55%) compared to topical exposure (15%), indicating a significant disparity in bee mortality between the two exposure routes. The 24 h post-treatment LC50 values for acetamiprid were 160.33 and 12.76 ppm for topical application and oral ingestion, respectively. The sublethal concentrations (LC10, LC20, and LC30) of acetamiprid were 15.23, 34.18, and 61.20 ppm, respectively, following topical exposure, and 2.85, 4.77, and 6.91 ppm, respectively, following oral exposure. The sublethal concentrations of acetamiprid significantly decreased learning during the 2nd-3rd conditioning trials and impaired memory formation at 2, 12, and 24 h following both topical and oral exposure routes, compared to the control bees. Notably, the sublethal concentrations were equally effective in impairing bee learning and memory. Taken together, acetamiprid exposure adversely affected bee survival, hindered learning, and impaired the memory retention of learned tasks.

Microfluidic Rheology: An Innovative Method for Viscosity Measurement of Gels and Various Pharmaceuticals.

Measuring the viscosity of pharmaceutical dosage forms is a crucial process. Viscosity provides information about the stability of the composition, the release rate of the drug, bioavailability, and, in the case of injectable drug formulations, even the force required for injection. However, measuring viscosity is a complex task with numerous challenges, especially for non-Newtonian materials, which include most pharmaceutical formulations, such as gels. Selecting the appropriate shear rate is critical. Since viscosity in many systems is highly temperature-dependent, stable temperature control is necessary during the measurement. Using microfluidics technology, it is now possible to perform rheological characterization and conduct fast and accurate measurements. Small sample volumes (even below 500 µL) are required, and viscosity determination can be carried out over a wide range of shear rates. Nevertheless, the pharmaceutical application of viscometers operating on the principle of microfluidics is not yet widespread. In our work, we compare the results of measurements taken with a microfluidic chip-based viscometer on different pharmaceutical forms (gels, solution) with those obtained using a traditional rotational viscometer, evaluating the relative advantages and disadvantages of the different methods. The microfluidics-based method enables time- and sample-efficient viscosity analysis of the examined pharmaceutical forms.

Insight into Current Practices of Community Pharmacists in Topical Corticosteroid Prescribing and Counseling: Cross-Sectional Survey Study from Saudi Arabia.

BACKGROUND: Topical corticosteroids are commonly used to treat several skin conditions, most notably atopic dermatitis. Many studies have found that patients lack knowledge about the safety, potency, and appropriate use of topical corticosteroids. This can be due to ineffective education by pharmacists and other healthcare providers. This study aims to evaluate the appropriateness of dispensing and counseling practices of community pharmacists towards topical corticosteroids in Saudi Arabia. METHODS: A cross-sectional survey study was conducted in Saudi Arabia among 418 community pharmacists from different regions of Saudi Arabia. Data were collected using a validated questionnaire that covered community pharmacists' sociodemographic information, their perceptions of patient knowledge about topical corticosteroid use, and their dispensing and their counseling practices, in addition to their perceived barriers to counseling. RESULTS: The majority of the participating community pharmacists were Saudi (57.4%), female (66.7%), holding a bachelor's degree (63.4%), and full-time workers (91.1%). Most of the time, community pharmacists counseled patients on the frequency of application per day and the duration of treatment (75.8% and 74.8%, respectively). The median counseling practice score was 17, with an IQR of 14-21. The main barrier to counseling was lack of time (33.7%). Only 15% of community pharmacists accurately identified all scenarios that necessitate medical referrals. Dry skin, itchiness, and irritation were the most common side effects reported by community pharmacists for patients to complain about (69.4%). Most pharmacists agreed that misuse is the most likely cause of topical corticosteroid adverse drug events (53.7%), followed by medication overuse, such as patient self-treatment (48%). CONCLUSION: Community pharmacists counseling practices to their patients about the use of topical corticosteroids require improvement. Continuing education and hands-on training are needed for community pharmacists regarding counseling about topical corticosteroids use.

Efficacy of topical drug application to manage in-office bleaching sensitivity: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: To answer whether the topical drug application can reduce in-office tooth bleaching sensitivity without impairing the color change. MATERIALS AND METHODS: This review was registered on PROSPERO (CRD42024524171). Two reviewers screened PubMed, Web of Science, Scopus, Embase, and clinicaltrials.gov in March 2024 independently for randomized clinical trials investigating the efficacy of topical drug application to manage in-office tooth bleaching sensitivity. The risk of bias was assessed using Cochrane's Risk of Bias tool (RoB2). Certainty of the evidence was assessed using the Grading of Recommendations: Assessment, Development, and Evaluation tool (GRADE). The meta-analyses evaluated the bleaching sensitivity and color change with RevMan 5.4 software. RESULTS: 334 articles were retrieved. The final sample was composed of four articles. Tested drugs were Otosporin, Eugenol, Ibuprofen with arginine, and Dipyrone. The meta-analysis evidenced no difference in bleaching sensitivity up to 1 h (MD, -0.39; 95% CI, -0.89, 0.11), 24 h (MD, -0.26, 95% CI, -0.71, 0.18), or 48 h (MD, 0.00, 95% CI, -0.16, 0.16). Meta-analysis for color change evidenced no difference for color change (MD, 0.03; 95% IC, -0.56, 0.61). The risk of bias was low. The certainty of the evidence was rated moderate for bleaching sensitivity and high for color change. CONCLUSIONS: Although topical drug application did not impair color change, it was ineffective in reducing in-office tooth bleaching sensitivity. CLINICAL RELEVANCE: topical drug application on dental enamel is not an effective approach in reducing bleaching sensitivity, but several modifications can be made in future studies to possibly achieve a better outcome.

Topical amlodipine-loaded solid lipid nanoparticles for enhanced burn wound healing: A repurposed approach.

Burn wounds are a complicated process with ongoing psychological and physical issues for the affected individuals. Wound healing consists of multifactorial molecular mechanisms and interactions involving; inflammation, proliferation, angiogenesis, and matrix remodeling. Amlodipine (ADB), widely used in cardiovascular disorders, demonstrated antioxidant and anti-inflammatory effects in some non-cardiovascular studies. It was reported that amlodipine is capable of promoting the healing process by regulation of collagen production, extracellular matrix, re-epithelialization and wound healing through its vasodilation and angiogenic activity. The objective of the current study is to appraise the wound healing capacity of amlodipine-loaded SLN (ADB-SLN) integrated into a hydrogel. The in-vitro characterization revealed that the optimized formulation was nanometric (190.4 ±â€¯1.6 nm) with sufficiently high entrapment efficiency (88 % ± 1.4) and sustained ADB release (85.45 ±â€¯4.45 % after 12 h). Furthermore, in-vivo evaluation was conducted on second-degree burns induced in male Sprague-Dawley rats. ADB-SLN gel revealed a high wound contraction rate and a significant improvement in skin regeneration and inflammatory biomarkers levels, confirming its efficiency in enhancing wound healing compared to other tested and commercial formulations. To conclude, the present findings proved that ADB-SLN integrated hydrogel offers a promising novel therapy for burn wound healing with a maximum therapeutic value.

Continuous negative-pressure wound therapy improves the survival rate of skin grafts and shortens the time required for skin graft survival.

BACKGROUND: The effectiveness of negative-pressure wound therapy (NPWT) in skin graft fixation has been demonstrated in several clinical studies. However, in vitro and in vivo studies on skin graft fixation with NPWT have been scarce. In this in vivo study, we aimed to determine whether NPWT fixation enhances skin graft survival and how it contributes to improving skin graft survival biologically. MATERIALS AND METHODS: We harvested skin from the bilateral abdominal wall of 88 mice after anesthetizing them. Full-thickness skin grafts (FTSGs) were performed on contralateral harvest sites, and grafts were fixed using NPWT (continuous and intermittent modes), conventional compression methods, and wrapping with polyurethane foam as a control group. On days 5 and 10 of grafting, the survival rates of the FTSGs were evaluated. Immunohistopathological analysis and measurement of the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and epidermal growth factor (EGF) were performed. RESULTS: The survival rates of FTSG in the continuous NPWT group were significantly higher than those in the other groups. The number of capillaries in the dermis was significantly higher in the continuous NPWT group than in the other groups. In the wound bed, VEGF levels were significantly higher in both NPWT groups than in the other groups. CONCLUSION: Continuous NPWT increases the survival rate of FTSGs and shortens the duration of skin graft survival.

Consensus statement from the AEDV Psoriasis Working Group (SWG) and Pediatric Working group (PWG) on the management of pediatric psoriasis. / Documento de consenso del Grupo Español de Psoriasis (GPS) y del grupo Español de Dermatología Pediátrica (GEDP) de la AEDV sobre el manejo de la psoriasis pediátrica.

Justification and objectives: The Spanish Academy of Dermatology and Venereology (AEDV) Psoriasis and Pediatric Working Groups (PSW and PWG) have developed a set of recommendations for the management of pediatric psoriasis based on the best available evidence and experts' opinion. Methodology: The methodology of nominal groups was followed, with help from a scoping review. A coordinator was designated, and a group of experts was selected based on their experience and knowledge on the management of psoriasis. The coordinator defined both the objectives and the key points of the document. Then, with help from a documentalist, a systematic literature review was conducted across Medline, Embase and Cochrane Library until May 2023. Systematic literature reviews, meta-analyses, and observational studies were included. National and international clinical practice guidelines and consensus documents were reviewed. With this information, the coordinator proposed preliminary recommendations that were discussed and modified in a nominal group meeting with all experts. After several review processes, which included an external review, the final document was generated. Results: Practical recommendations on the evaluation and management of patients with pediatric psoriasis are presented in association with other AEDV documents. The evaluation of the pediatric patient, the definition of the therapeutic objectives, the criteria for indication and selection of treatment are addressed. Practical issues such as therapeutic failure, response maintenance, comorbidity and risk management are also included.

Preliminary assessment of blood mercury contamination in four African crocodile species.

Heavy metal contamination in the environment is an increasingly pervasive threat to the long-term persistence of wildlife. As high trophic level consumers, crocodylians are at substantial risk from bioaccumulation of mercury (Hg). Despite that they are generally well-studied and the focal species of many conservation efforts around the world, little is known about Hg contamination levels in most crocodylians. Here we preliminarily evaluate blood Hg contamination in four African species - Central African slender-snouted crocodile (Mecistops leptorhynchus), African dwarf crocodile (Osteolaemus tetraspis), West African crocodile (Crocodylus suchus), and Nile crocodile (Crocodylus niloticus) - from a diversity of sites and habitats across 5 different countries representing varying degrees of environmental pollution. All of our sampled crocodiles were Hg contaminated and, worryingly, these African crocodiles generally showed the highest levels of Hg contamination of any crocodylian species examined to date. Of most concern was that Hg concentrations were not only highest in M. leptorhynchus, the most threatened amongst our study species, but also in individuals sampled in what are believed to be some of the most remote and pristine natural areas left in Africa - Gabon's national parks. Our results underscore the need to better understand the impact of longstanding petroleum, mining, forestry, and agricultural industries on the entire aquatic food chain throughout much of Africa, including on the threatened species in these habitats and the human populations that depend on them for their subsistence and livelihoods.

Adult Female Acne: Managing the Hormones.

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.

Therapeutic-driven framework for bioequivalence assessment of complex topical generic drug products.

Despite the continuous research on understanding how topical drugs and the skin interact, the development of a topical generic product remains a challenge. Due to their local action effect rather than systemic, establishing suitable frameworks for documenting bioequivalence between reference and test formulations is anything but straightforward. In previous years, clinical endpoint trials were considered the gold standard method to demonstrate bioequivalence between topical products. Nevertheless, significant financial and time resources were required to be allocated owing to the inherent complexity of these studies. To address this problem, regulatory authorities have begun to accept alternative approaches that could lead to a biowaiver, avoiding the need for clinical endpoint trials. These alternatives encompass various in vitro and/or in vivo techniques that have been analysed and the benefits and drawbacks of each method have been considered. Furthermore, other factors like the integration of a quality by design framework to ensure a comprehensive understanding of the product and process quality attributes have also been taken into account. This review delves into international regulatory recommendations for semisolid topical products, with a focus on those established by the European Medicines Agency, as well as the Food and Drug Administration. Both approaches were carefully examined, discussing aspects such as acceptance criteria, sample size, and microstructure evaluation. Additionally, novel and innovative therapeutic-driven approaches based on in vitro disease models for the rapid and effective development of topical generic products are presented.

Atropine: Updates on myopia pharmacotherapy.

The prevalence of myopia has rapidly increased over the last 30 years, with the World Health Organization estimating a worldwide incidence of 23%, projected to increase to 50% by 2050. The myopia epidemic has prompted a reincarnation in efforts to overcome this challenge. The exploration of atropine use in myopia was a result due to a lack of treatment in effect. This study aimed at reviewing the role of atropine in the management of myopia worldwide based on currently available findings. A literature search was conducted using PubMed/MEDLINE and Google Scholar for studies published up to April 2022 inclusive. Articles with high or medium clinical relevance were selected for this review. Multiple studies have demonstrated the relevance and efficacy rates of different concentrations of atropine, despite still insufficiently explained the exact site and mechanism of action of atropine in slowing myopia progression. Currently available findings highlight that topical atropine opened a new page in pharmacotherapy of myopia and have shown a high therapeutic effect on myopia progression in Asian and European child population, irrespective of ethnicity. There is potential for myopia control with fewer side effects using lower concentrations but still exists a room for improvement, underscoring the requirement of modified atropine topical preparations with increased bioavailability, potentially with nanoparticle formulations, to enable the effective management of myopia.

Methylene Blue, a Unique Topical Analgesic: A Case Report.

Background: Rectal prolapse is a circumferential, full-thickness protrusion of the rectum through the anus, which, if not properly managed, may become incarcerated and pose a risk of strangulation. This pathology is rarely a medical emergency unless a complication is encountered. Such complications include infection, necrosis, perforation, incarceration, and uncontrolled pain. Case Presentation: We report a case of an elderly patient with pain associated with chronic rectal prolapse. Surgical intervention had been ruled out, and there had been no pain relief after using systemic analgesics. Case Management: Based on increasing reports of analgesic properties, topical methylene blue (MB) 0.1% was applied externally at the prolapsed organ, obtaining pain relief. Case Outcome: The patient experienced immediate and long-lasting pain relief; MB applications were continued every 12 hours as needed. After this therapy, the patient was no longer in need of systemic analgesics. No side effects were reported. Conclusion: Topical MB may be an effective analgesic for the management of pain associated with chronic rectal prolapse. This treatment might be extrapolated to other clinical scenarios of tegumentary pain. Similar use has been shown to be safe and effective in other pathologies, including pain in oral mucositis associated with cancer therapy.

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Hyaluron-Based Bionanocomposites of Silver Nanoparticles with Graphene Oxide as Effective Growth Inhibitors of Wound-Derived Bacteria.

Keeping wounds clean in small animals is a big challenge, which is why they often become infected, creating a risk of transmission to animal owners. Therefore, it is crucial to search for new biocompatible materials that have the potential to be used in smart wound dressings with both wound healing and bacteriostatic properties to prevent infection. In our previous work, we obtained innovative hyaluronate matrix-based bionanocomposites containing nanosilver and nanosilver/graphene oxide (Hyal/Ag and Hyal/Ag/GO). This study aimed to thoroughly examine the bacteriostatic properties of foils containing the previously developed bionanocomposites. The bacteriostatic activity was assessed in vitro on 88 Gram-positive (n = 51) and Gram-negative (n = 37) bacteria isolated from wounds of small animals and whose antimicrobial resistance patterns and resistance mechanisms were examined in an earlier study. Here, 69.32% of bacterial growth was inhibited by Hyal/Ag and 81.82% by Hyal/Ag/GO. The bionanocomposites appeared more effective against Gram-negative bacteria (growth inhibition of 75.68% and 89.19% by Hyal/Ag and Hyal/Ag/Go, respectively). The effectiveness of Hyal/Ag/GO against Gram-positive bacteria was also high (inhibition of 80.39% of strains), while Hyal/Ag inhibited the growth of 64.71% of Gram-positive bacteria. The effectiveness of Hyal/Ag and Hyal/Ag/Go varied depending on bacterial genus and species. Proteus (Gram-negative) and Enterococcus (Gram-positive) appeared to be the least susceptible to the bionanocomposites. Hyal/Ag most effectively inhibited the growth of non-pathogenic Gram-positive Sporosarcina luteola and Gram-negative Acinetobacter. Hyal/Ag/GO was most effective against Gram-positive Streptococcus and Gram-negative Moraxella osloensis. The Hyal/Ag/GO bionanocomposites proved to be very promising new antibacterial, biocompatible materials that could be used in the production of bioactive wound dressings.

Formulation and characterization of antibiotic drug loaded aquasome for the topical application.

Aim: This study aimed to develop a topical antibiotic drug delivery system using aquasomes for enhanced treatment of skin and soft tissue infections (SSTIs). Materials & methods: Cephalothin was loaded into aquasomes using a multi-step process and optimized using design of experiment. The aquasomes were characterized for FT-IR, SEM and zeta potential analysis. Entrapment efficacy, In vitro drug release studies, antibacterial assays and stability study was performed to evaluate the efficacy of the formulated aquasomes. Results & conclusion: The formulated cephalothin-loaded aquasomes exhibited stable properties, controlled drug release and significant antibacterial activity against bacteria. This proves that the developed aquasome-based delivery system has the potential for sustained treatment of SSTIs.

Cephalothin is a medicine that helps fight bacteria, but it doesn't work well on the skin because it does not come in a gel form. We created a special way, called a magic vehicle, to help the medicine reach the skin better. Infections on the skin and in soft tissues, caused by germs. We found that our new way of giving the medicine is small, strong and fights germs very well. This could be a great way to treat skin infections and help people feel better.

Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells.

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). Topical tirbanibulin has clinically resolved HPV-57 ( +) squamous cell carcinoma (SCC), HPV-16 ( +) vulvar high-grade squamous intraepithelial lesion, epidermodysplasia verruciformis, and condyloma. We examined how tirbanibulin might affect HPV oncoprotein expression and affect other cellular pathways involved in cell proliferation and transformation. We treated the HeLa cell line, containing integrated HPV-18, with increasing doses of tirbanibulin to determine the effects on cell proliferation. Immunoblotting was performed with antibodies against the Src canonical pathway, HPV 18 E6 and E7 transcription regulation, apoptosis, and invasion and metastasis pathways. Cell proliferation assays with tirbanibulin determined the half-maximal inhibitory concentration (IC50) of HeLa cells to be 31.49 nmol/L. Increasing concentrations of tirbanibulin downregulates the protein expression of Src (p < 0.001), phospho-Src (p < 0.001), Ras (p < 0.01), c-Raf (p < 0.001), ERK1 (p < 0.001), phospho-ERK1 (p < 0.001), phospho-ERK2 (p < 0.01), phospho-Mnk1 (p < 0.001), eIF4E (p < 0.01), phospho-eIF4E (p < 0.001), E6 (p < 0.01), E7 (p < 0.01), Rb (p < 0.01), phospho-Rb (p < 0.001), MDM2 (p < 0.01), E2F1 (p < 0.001), phospho-FAK (p < 0.001), phospho-p130 Cas (p < 0.001), Mcl-1 (p < 0.01), and Bcl-2 (p < 0.001), but upregulates cPARP (p < 0.001), and cPARP/fPARP (p < 0.001). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.

Tirbanibulin is Promising Novel Therapy for Human Papillomavirus (HPV)-associated Diseases.Tirbanibulin 1% ointment is an approved synthetic topical ointment for treating actinic keratoses (AK), a precancer of skin cancer. Topical tirbanibulin has previously been reported to clinically resolve human papillomavirus (HPV)-( +) diseases.In this study, we examine how tirbanibulin may affect the HPV and pathways associated with cancer.We treated the HeLa cell line to determine the effects on HPV cell proliferation. Increasing the concentration of tirbanibulin statistically significantly affected numerous cellular pathways often associated with cancer.These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins and thereby kill cancer cells.