Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study.

Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.

Feeding the Body Through the Skin: Ethosomes and Transethosomes as a New Topical Delivery System for Bioactive Compounds.

Because the feeding of our body through the oral route can be associated with many drawbacks due to the degradation of natural molecules during transit in the gastrointestinal tract, a transdermal delivery strategy, usually employed in the pharmaceutical field, can present an effective alternative for delivery of bioactives and nutrients from foods. In this review, the chance to feed the body with nutritive and bioactive molecules from food through transdermal administration is discussed. Various nanotechnological devices employed for topical and transdermal delivery of bioactive compounds are described. In addition, mechanisms underlying their potential use in the delivery of nutritive molecules, as well as their capability to efficaciously reach the dermis and promote systemic distribution, are detailed.

Progress in Topical and Transdermal Drug Delivery Research-Focus on Nanoformulations.

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems.

Evidence of Cannabidiol Effectiveness Associated or Not with Tetrahydrocannabinol in Topical Administration: A Scope Review.

Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.

Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation.

The ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm2 after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions.

Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections.

BACKGROUND: In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections. METHODS: We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023. RESULTS: Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects. CONCLUSION: The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

Validation of the Index for Facial Angiofibromas: Data analysis from a randomized controlled trial of sirolimus gel treatment in patients with tuberous sclerosis complex.

The Index for Facial Angiofibromas (IFA), a novel scoring system for angiofibromas, has been validated in patients with tuberous sclerosis complex (TSC). The objective of this analysis was to further validate the IFA using data from a clinical trial of topical sirolimus in patients with TSC. This was an analysis of photographs from a Phase III trial conducted in Japan (NCT02635789). Patients (n = 62) were randomized 1:1 to receive sirolimus or placebo gel for 12 weeks. Changes in angiofibromas were independently assessed using the primary composite endpoint, the Facial Angiofibroma Severity Index (FASI), and the IFA. Thresholds for a clinically meaningful change in IFA score were evaluated using receiver operating characteristic (ROC) analysis. The IFA scores had good-to-excellent inter-assessor reliability, very high intra-assessor reliability, and could be used to evaluate the distribution of disease severity at baseline. High correlations were observed between the categorized change from baseline in IFA scores and the primary composite endpoint (Kendall's coefficient of concordance, W = 0.8655, p < 0.0001), and between the change from baseline in IFA and FASI scores (Kendall's coefficient of concordance, W = 0.745, p < 0.0001). By ROC analysis, an optimal IFA cut-off point of 1.667 was determined to distinguish patients with markedly improved or improved angiofibromas from those with slightly improved or unchanged angiofibromas (area under the curve 0.937) as determined by the primary composite endpoint. The IFA score is potentially clinically useful because of its high validity and reliability. A decrease in score from baseline of ≥1.667 may be considered clinically meaningful.

Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.

Local Oxygen-Based Therapy (blue®m) for Treatment of Peri-Implant Disease: Clinical Case Presentation and Review of Literature about Conventional Local Adjunct Therapies.

Peri-implant diseases including peri-implant mucositis and peri-implantitis are among the major causes of failure of implant-supported dental restorations. They are characterized by progressive inflammation of the peri-implant mucosa, extending to the surrounding connective tissues and leading to bone loss and implant failure. Although strict oral hygiene practices help in preventing peri-implant diseases, plaque buildup around the implant restoration leads to chronic inflammation, due to the adherent bacterial biofilm. While mechanical debridement and non-surgical therapy to remove inflamed connective tissue (ICT) form the mainstay of treatment, additional local adjunctive therapies enhance clinical outcomes. Topical oxygen therapy is known to reduce inflammation, increase vascularity, and act as a bacteriostatic measure. The use of oxygen-based therapy (blue®m) products as a local adjunctive therapy for peri-implant mucositis and peri-implantitis can result in clinical outcomes similar to that of conventional local adjuncts such as chlorhexidine, antibiotics, and antibacterial agents. This report aims to present the clinical findings of patients with peri-implant mucositis and peri-implantitis, who were managed using local oxygen-based therapy as an adjunct to non-surgical therapy. In addition, a review of the literature about commonly used local adjuncts for peri-implant diseases has been included in the report to provide a means of comparison between conventional local adjunct therapy and topical oxygen-based therapy. Based on the reported findings and reviewed literature, local oxygen-based adjunct therapy was equally effective as conventionally used local adjuncts such as antibiotics, antibacterials, and probiotics, in treating patients with peri-implant diseases.

A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation.

The objective of the present study was to develop and evaluate NLC-chitosan hydrogel beads for topical administration. The feasibility of the preparation technology was verified by investigating various formulation factors and the impact of chitosan hydrogel beads on the NLC. The encapsulation efficiency of NLC-chitosan hydrogel beads was above 95% in optimized process conditions. The physical characterization of the NLC-chitosan hydrogel beads showed that the NLC was distributed within the network of the chitosan hydrogel beads. Furthermore, the incorporation of NLC into the chitosan hydrogel beads was related to the electrostatic interaction between the surface of the NLC and chitosan, which influenced the lipid ordering degree of the NLC and contributed to the stability. The stability studies showed that the retention rate of quercetin in the NLC-chitosan hydrogel beads was 88.63 ± 2.57% after 10 months of storage under natural daylight. An in vitro permeation study showed that NLC-chitosan hydrogel beads exhibited superior ability in enhancing skin permeation by hydrophobic active ingredients compared to the NLC and significantly increased skin accumulation. These studies demonstrated that the use of NLC-chitosan hydrogel beads might be a promising strategy for the delivery of hydrophobic active ingredients in topical administration.

Nonlinear Pharmacokinetics of Topical Flurbiprofen Gel in a Phase I Study Among Chinese Healthy Adults.

INTRODUCTION: PDX-02 (Flurbiprofen sodium) is a topical nonsteroidal anti-inflammatory drug in gel formulation for local analgesia and anti-inflammation. A Phase I clinical trial was conducted to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of PDX-02 gel in Chinese healthy adults. METHODS: The trial comprised three parts: (1) a single-dose ascending study with three dose levels (0.5%, 1% to 2% PDX-02 gel) applied on a 136 cm2 skin area; (2) a multiple-dose study with either 1% or 2% PDX-02 gel applied on a 136 cm2 skin area for 7 consecutive days; and (3) a high dose group with 2% PDX-02 gel on an 816 cm2 skin area and a frequent multiple dose group with 2% PDX-02 gel on a 272 cm2 skin area four times a day for 7 consecutive days. The safety, tolerability and pharmacokinetics of the PDX-02 gel were evaluated in each part. RESULTS: A total of sixty participants completed the trial, with all adverse events recovered and all positive skin reaction being transient and recovered. The overall absorption of topical PDX-02 gel was slow with a mean peak time exceeding 9 h. The elimination rate remained consistent between dose groups. A less-than-dose-proportional nonlinear pharmacokinetics relationship was observed within the studied dose range, and this is likely due to the autoinduction of skin first-pass metabolism. CONCLUSION: The topical PDX-02 gel showed favorable safety and tolerability in both single and multiple dosing studies, with a less-than-dose-proportional nonlinear pharmacokinetics observed.

CFD simulation of cannabidiol delivery through microneedle patches.

This study investigates the efficiency and influence of microneedle parameters, specifically Needle Point Angle (a) and Needle Height (h), on the diffusion of Cannabidiol (CBD) across varying skin depths. Utilizing the Latin Hypercube Sampling method, twelve distinct cases were analyzed. Observations reveal a consistent high concentration of CBD delivered via the microneedle patch, with a notable decrease in concentration as the depth increases, displaying a non-linear trend. Multivariate polynomial regression offers a quantitative relationship between the variables, with the third-order bivariate fitting providing the most accurate representation. Compared to other CBD delivery mechanisms, microneedle patches present enhanced CBD concentrations, circumventing challenges faced by other methods such as dosage inaccuracy, systemic absorption issues, and CBD degradation. The results highlight the potential of microneedle patches as a promising avenue for optimized transdermal drug delivery.

Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis.

OBJECTIVE: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide-releasing medication) versus vehicle in MC patients with or without AD. METHODS: Three Phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group trials (B-SIMPLE[berdazimer sodium in molluscum patients with lesions]1, -2, -4) enrolled patients 6 months and older with 3-70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta-analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD- when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. RESULTS: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD- (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7-2.5) and AD- (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4-2.4) subgroups. AEs in AD+ were application-site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). CONCLUSIONS: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer-induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum.

Beyond the adverse effects of the systemic route: Exploiting nanocarriers for the topical treatment of skin cancers.

Skin cancer is a heterogeneous disease that can be divided into two main groups, melanoma and nonmelanoma skin cancers. Conventional therapies for skin cancer have numerous systemic side effects and a high recurrence rate. Topical treatment is an alternative approach, but drug permeability remains a challenge. Therefore, nanocarriers appear as important nanotechnology tools that reduces both the side effects and improves clinical outcomes. This is why they are attracting growing interest. In this review, scientific articles on the use of nanocarriers for the topical treatment of skin cancer were collected. Despite the promising results of the presented nanocarriers and considering that some of them are already on the market, there is an urgent need for investment in the development of manufacturing methods, as well as of suitable toxicological and regulatory evaluations, since the conventional methods currently used to develop these nanocarriers-based products are more time-consuming and expensive than conventional products.

[Localized scleroderma]. / Lokalisierte Sklerodermie.

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises a heterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. A distinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. A detailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with a prominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

Local Low-dose Anti-PD-L1 Antibodies Improve Antitumor Effects in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors are highly effective for treating recurrent and metastatic head and neck cancers. However, they require systemic administration and are associated with immune-related adverse events (irAEs). Reducing therapeutic antibody doses to prevent irAEs is challenging. MATERIALS AND METHODS: Mouse buccal mucosa squamous cell carcinoma cells (Sq-1979) were transplanted into the backs of mice to induce tumors. The antitumor efficacy and tumor immunohistological environment in tumor-bearing mice were compared after administering a standard dose of programmed death-ligand 1 (PD-L1) antibodies systemically (200 mg/body) or 1/10th of the standard dose (20 mg/body) directly to tumors. Mice received four doses of antibody administered in 3-day intervals. Tumor reduction rates and antitumor efficacies were evaluated 21 days after initiating treatment. CD8+T cell counts and PD-L1, PD-1, perforin, and granzyme B levels; CD25 and Foxp3 expression levels; and tumor Tregs were assessed in the resected subcutaneous tumors. RESULTS: The antitumor efficacies in the local low-dose and systemic standard-dose groups were compared with that of the control group. The efficacies of the two treatment groups were similar, and both treatment groups revealed significant antitumor effects compared to the control group. Perforin and granzyme B levels were higher in the local low-dose group (p<0.05). CONCLUSION: Local low-dose administration of anti-PD-L1 antibodies exhibits antitumor efficacy similar to systemic standard-dose administration suggesting that local low-dose administration is useful for treating oral squamous cell carcinoma.

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis.

Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes. Currently, there is no cure for any of the EB subtypes associated with various mutations. Existing therapies primarily focus on alleviating pain and promoting early wound healing to prevent potential complications. Consequently, there is an urgent need for innovative therapeutic approaches. The objective of this research was to assess the efficacy of various topical treatments in patients with EB with the goal of achieving wound healing. A secondary objective was to analyse the efficacy of topical treatments for symptom reduction. A literature search was conducted using scientific databases, including The Cochrane Library, Medline (Pubmed), Web of Science, CINHAL, Embase, and Scopus. The protocol review was registered in PROSPERO (ID: 418790), and inclusion and exclusion criteria were applied, resulting in the selection of 23 articles. Enhanced healing times were observed compared with the control group. No conclusive data have been observed on pain management, infection, pruritus episodes, and cure rates over time. Additionally, evidence indicates significant progress in gene therapies (B-VEC), as well as cell and protein therapies. The dressing group, Oleogel S-10, allantoin and diacerein 1%, were the most represented, followed by fibroblast utilisation. In addition, emerging treatments that improve the patient's innate immunity, such as calcipotriol, are gaining attention. However, more trials are needed to reduce the prevalence of blistering and improve the quality of life of individuals with epidermolysis bullosa.

Novel Therapeutic Hybrid Systems Using Hydrogels and Nanotechnology: A Focus on Nanoemulgels for the Treatment of Skin Diseases.

Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions.

Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials.

BACKGROUND: An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. OBJECTIVE: To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide-releasing medication) versus vehicle. METHODS: Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. RESULTS: There were 1598 patients enrolled (n = 917 berdazimer, n = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, P < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. LIMITATIONS: Berdazimer sodium in molluscum patients with lesions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. CONCLUSIONS: Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.