The Role of Quercetin as a Plant-Derived Bioactive Agent in Preventive Medicine and Treatment in Skin Disorders.

Quercetin, a bioactive plant flavonoid, is an antioxidant, and as such it exhibits numerous beneficial properties including anti-inflammatory, antiallergic, antibacterial and antiviral activity. It occurs naturally in fruit and vegetables such as apples, blueberries, cranberries, lettuce, and is present in plant waste such as onion peel or grape pomace which constitute good sources of quercetin for technological or pharmaceutical purposes. The presented study focuses on the role of quercetin in prevention and treatment of dermatological diseases analyzing its effect at a molecular level, its signal transduction and metabolism. Presented aspects of quercetin potential for skin treatment include protection against aging and UV radiation, stimulation of wound healing, reduction in melanogenesis, and prevention of skin oxidation. The article discusses quercetin sources (plant waste products included), methods of its medical administration, and perspectives for its further use in dermatology and diet therapy.

A case report on acquired reactive perforating collagenosis.

INTRODUCTION: Acquired reactive perforating collagenosis (ARPC) is a rare perforating skin disease with unclear pathogenesis, often leading to misdiagnosis. Utilizing noninvasive skin microscopy improves diagnostic accuracy while reducing misdiagnosis rates. PATIENT CONCERNS: Given its association with systemic diseases, comprehensive examinations are crucial for early detection of related diseases such as tumors. Clinically, it still lacks standardized guidelines for the treatment. Clinical treatment is mostly based on symptomatic treatment. Oral administration of pregabalin capsules can significantly relieve itching symptoms, and narrow-wave ultraviolet irradiation can accelerate the recovery of skin lesions. DIAGNOSIS: Dermoscopy and skin biopsy was used to confirm this case was ARPC. INTERVENTIONS: Treatment was based on oral administration of 20 mg prednisone, 1 tablet of loratadine, 1 tablet of pregabalin in the morning and evening, and external application of halomethasone ointment. OUTCOMES: Itching symptoms were significantly relieved. CONCLUSION: This case report demonstrates that clinical dermoscopy can improve the diagnosis rate of ARPC, and pregabalin capsules can significantly relieve itching symptoms.

An Overview of Methotrexate Indications in Skin Diseases.

Methotrexate is an immunosuppressive drug with remarkable therapeutic results in the treatment of autoimmune and proliferative skin diseases. Although it has been more than half a century since it was first introduced into the therapeutic arsenal of dermatologists, there are currently no standardized therapeutic protocols regarding the prescription of methotrexate in dermatology, with the exception of psoriasis treatment. This review aims to highlight the indications and benefits of methotrexate beyond psoriasis, with a focus on a wide range of inflammatory, vesiculobullous, and proliferative dermatological pathologies.

Breaking barriers: Innovative approaches for skin delivery of RNA therapeutics.

RNA therapeutics represent a rapidly expanding platform with game-changing prospects in personalized medicine. The disruptive potential of this technology will overhaul the standard of care with reference to both primary and specialty care. To date, RNA therapeutics have mostly been delivered parenterally via injection, but topical administration followed by intradermal or transdermal delivery represents an attractive method that is convenient to patients and minimally invasive. The skin barrier, particularly the lipid-rich stratum corneum, presents a significant hurdle to the uptake of large, charged oligonucleotide drugs. Therapeutic oligonucleotides need to be engineered for stability and specificity and formulated with state-of-the-art delivery strategies for efficient uptake. This review will cover various passive and active strategies deployed to enhance permeation through the stratum corneum and achieve effective delivery of RNA therapeutics to treat both local skin disorders and systemic diseases. Some strategies to achieve selectivity between local and systemic administration will also be discussed.

Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery.

Skin diseases pose challenges in treatment due to the skin's complex structure and protective functions. Topical drug delivery has emerged as a preferred method for treating these conditions, offering localized therapy with minimal systemic side effects. However, the skin's barrier properties frequently limit topical treatments' efficacy by preventing drug penetration into deeper skin layers. In recent years, laser-assisted drug delivery (LADD) has gained attention as a promising strategy to overcome these limitations. LADD involves using lasers to create microchannels in the skin, facilitating the deposition of drugs and enhancing their penetration into the target tissue. Several lasers, such as fractional CO2, have been tested to see how well they work at delivering drugs. Despite the promising outcomes demonstrated in preclinical and clinical studies, several challenges persist in implementing LADD, including limited penetration depth, potential tissue damage, and the cost of LADD systems. Furthermore, selecting appropriate laser parameters and drug formulations is crucial to ensuring optimal therapeutic outcomes. Nevertheless, LADD holds significant potential for improving treatment efficacy for various skin conditions, including skin cancers, scars, and dermatological disorders. Future research efforts should focus on optimizing LADD techniques, addressing safety concerns, and exploring novel drug formulations to maximize the therapeutic benefits of this innovative approach. With continued advancements in laser technology and pharmaceutical science, LADD has the potential to revolutionize the field of dermatology and enhance patient care.

Cutaneous Rosai-Dorfman disease: a systematic review and reappraisal of its treatment and prognosis.

Cutaneous Rosai Dorfman disease (CRDD) is a rare histiocytic disorder that shows distinctive clinical presentation and prognosis. Sufficient data is currently lacking regarding evidence-based management of CRDD. This systematic review aims to provide a comprehensive overview of CRDD, focusing on treatment approaches and outcomes. PubMed and Scopus databases were searched for studies on CRDD from June 1st, 2013 to May 31st, 2023. Articles describing cases of CRDD confirmed with histological examination were eligible for inclusion. All interventions for CRDD were analyzed. The primary outcome measure was the response of cutaneous lesions to treatment including complete response (CR), partial response (PR), and no response. The secondary outcome measures were mortality rate, relapse rate, and the occurrence of adverse events related to CRDD treatment. Eighty-seven articles describing 118 CRDD cases were included. The mean age was 48.2±16.8 years. The sex ratio (F/M) was 1.53. Nodular (46.6%) erythematous (45.3%) lesions, located on the face (38.1%) were the most prevalent presentations. Associated hematological malignancies were noted in 8 (6.8%) cases. Surgical excision was the most prevalent intervention (51 cases) with CR in 48 cases. Systemic corticosteroids were used in 32 cases with 20 CR/PR, retinoids in 10 cases with 4 CR/PR, thalidomide in 9 cases with 5 CR/PR, methotrexate in 8 cases with 7 CR/PR while observation was decided in 10 cases with 6 CR/PR. Factors independently associated with the absence of response to treatment were facial involvement (OR = 0.76, p = 0.014), and cutaneous lesion size (OR = 1.016, p = 0.03). This systematic review shows distinctive clinical characteristics of CRDD and provides insights into the appropriate management of the disease. It allowed a proposal of a treatment algorithm that should be interpreted in the context of current evidence and would help practitioners in treating this rare disease.

Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases.

Inflammatory skin diseases highlight inflammation as a central driver of skin pathologies, involving a multiplicity of mediators and cell types, including immune and non-immune cells. Adenosine, a ubiquitous endogenous immune modulator, generated from adenosine triphosphate (ATP), acts via four G protein-coupled receptors (A1, A2A, A2B, and A3). Given the widespread expression of those receptors and their regulatory effects on multiple immune signaling pathways, targeting adenosine receptors emerges as a compelling strategy for anti-inflammatory intervention. Animal models of psoriasis, contact hypersensitivity (CHS), and other dermatitis have elucidated the involvement of adenosine receptors in the pathogenesis of these conditions. Targeting adenosine receptors is effective in attenuating inflammation and remodeling the epidermal structure, potentially showing synergistic effects with fewer adverse effects when combined with conventional therapies. What is noteworthy are the promising outcomes observed with A2A agonists in animal models and ongoing clinical trials investigating A3 agonists, underscoring a potential therapeutic approach for the management of inflammatory skin disorders.

The potential of RNA therapeutics in dermatology.

Ribonucleic acid (RNA) therapeutics hold great potential for the advancement of dermatological treatments due to, among other reasons, the possibility of treating previously undruggable targets, high specificity with minimal side effects, and ability to include multiple RNA targets in a single product. Although there have been research relating to RNA therapeutics for decades, there have not been many products translated for clinical use until recently. This may be because of challenges to the application of RNA therapeutics, including the dearth of effective modes of delivery to the target, and rapid degradation of RNA in the human body and environment. This article aims to provide insight on (1) the wide-ranging possibilities of RNA therapeutics in the field of dermatology as well as (2) how key challenges can be addressed, so as to encourage the development of novel dermatological treatments. We also share our experience on how RNA therapeutics have been applied in the management of hypertrophic and keloid scars.

Formulation development of tazarotene-loaded PLGA nanoparticles for follicular delivery in the treatment of inflammatory skin diseases.

Tazarotene is a widely prescribed topical retinoid for acne vulgaris and plaque psoriasis and is associated with skin irritation, dryness, flaking, and photosensitivity. In vitro permeation of tazarotene was studied across the dermatomed human and full-thickness porcine skin. The conversion of tazarotene to the active form tazarotenic acid was studied in various skin models. Tazarotene-loaded PLGA nanoparticles were prepared using the nanoprecipitation technique to target skin and hair follicles effectively. The effect of formulation and processing variables on nanoparticle properties, such as particle size and drug loading, was investigated. The optimized nanoparticle batches with particle size <500 µm were characterized further for FT-IR analysis, which indicated no interactions between tazarotene and PLGA. Scanning electron microscopy analysis showed uniform, spherical, and non-agglomerated nanoparticles. In vitro release study using a dialysis membrane indicated a sustained release of 40-70 % for different batches over 36 h, following a diffusion-based release mechanism based on the Higuchi model. In vitro permeation testing (IVPT) in full-thickness porcine skin showed significantly enhanced follicular and skin delivery from nanoparticles compared to solution. The presence of tazarotenic acid in the skin from tazarotene nanoparticles indicated the effectiveness of nanoparticle formulations in retaining bioconversion ability and targeting follicular delivery.

Recombinant scFv-Fc Anti-kallikrein 7 Antibody-Loaded Thermosensitive Hydrogels Against Skin Desquamation Disorders.

Human tissue kallikrein-related peptidase 7 (KLK7) is a serine protease implicated in the physiology of skin desquamation, and its uncontrolled activity can lead to chronic diseases such as psoriasis, atopic dermatitis, and Netherton syndrome. For this reason, kallikrein 7 has been identified as a potential therapeutic target. This work aimed to evaluate Pluronic (PL) hydrogels as topical carriers of four specific scFv-Fc antibodies to inhibit KLK7. The hydrogels comprised PL F127 (30% w/v) alone and a binary F127/P123 (28-2% w/v) system. Each formulation was loaded with 1 µg/mL of each antibody and characterized by physicochemical and pharmaceutical techniques, considering antibody-micelle interactions and hydrogel behavior as smart delivery systems. Results showed that the antibodies were successfully loaded into the PL-based systems, and the sol-gel transition temperature was shifted to high values after the P123 addition. The antibodies released from the gels preserved their rheological properties (G' > G'', 35- to 41-fold) and inhibitory activity against KLK7, even after 24 h. This work presented potential agents targeting KLK7 that may provide strategies for treating skin abnormalities.

Effectiveness of topical hyaluronic acid of different molecular weights in xerosis cutis treatment in elderly: a double-blind, randomized controlled trial.

Dry skin is a common dermatological condition that frequently affects the elderly. A contributing cause to dry skin is a reduced concentration of hyaluronic acid (HA) in both the epidermis and dermis. The effectiveness of moisturizer containing HA as a therapy for dry skin is impacted by its specific molecular weight. Low molecular weight HA (LMWHA) is believed to be more effective in replenishing skin hydration in aging skin compared to High Molecular Weight HA (HMWHA) due to its ability to penetrate the stratum corneum. However, there is a lack of clinical research supporting this claim. A double-blind, randomized controlled trial was conducted on 36 residents of a nursing home in Jakarta. The participants, aged between 60 and 80 years, had been diagnosed with dry skin. Each test subject was administered three distinct, randomized moisturizing lotions (LMWHA, HMWHA, or vehicle), to be topically applied to three separate sites on the leg. Skin capacitance (SCap), transepidermal water loss (TEWL), and specified symptom sum score (SRRC) were measured at weeks 0, 2, and 4. After four weeks of therapy, area that was treated with LMWHA showed greater SCap values compared to the area treated with HMWHA (56.37 AU vs. 52.37 AU, p = 0.004) and vehicle (56.37 AU vs. 49.01 AU, p < 0.001). All groups did not show any significant differences in TEWL and SRRC scores. No side effects were found in all groups. The application of a moisturizer containing LMWHA to the dry skin of elderly resulted in significant improvements in skin hydration compared to moisturizers containing HMWHA and vehicle. Furthermore, these moisturizers demonstrated similar safety in treating dry skin in the elderly. ClinicalTrials.gov Identifier NCT06178367, https://clinicaltrials.gov/study/NCT06178367 .

Beclomethasone loaded liposomes enriched with mucin: A suitable approach for the control of skin disorders.

Inflammatory skin disorders are the fourth leading cause of chronic non-fatal conditions, which have a serious impact on the patient quality of life. Due to their treatment with conventional corticosteroids, which often result in poor therapeutic efficacy, relapses and systemic side effects from prolonged therapy, these diseases represent a global burden that negatively impacts the global economy. To avoid these problems and optimize corticosteroid benefits, beclomethasone was loaded into liposome formulations specifically tailored for skin delivery. These formulations were enhanced with mucin (0.1 and 0.5 % w/v) to further ensure prolonged formulation permanence at the site of application. The addition of 0.5 % w/v mucin resulted in the formation of small unilamellar vesicles and multicompartment vesicles. Liposomes and 1mucin-liposomes were smaller (∼48 and ∼61 nm, respectively) and more monodispersed (PI ∼ 0.14 and ∼ 0.17, respectively) than 5mucin-liposomes, which were larger (∼137 nm), slightly polydispersed (PI ∼ 0.23), and less stable during storage (4 months in the dark at 25 °C). Liposomes were negatively charged (∼ -79 mV) irrespective of their composition, and capable of incorporating high amount of beclomethasone (∼ 80 %). In vitro studies on skin fibroblasts and keratinocytes confirmed the high biocompatibility of all formulations (viability ≥ 95 %). However, the use of mucin-liposomes resulted in higher efficacy against nitric oxide production and free radical damage. Finally, topical applications using 12-O-tetradecanoylphorbol-13-acetate-injured skin in vivo experiments showed that only the mucin-enriched formulations could restore healthy conditions within 4 days, underscoring promise as a treatment for skin disorders.

Recent advances of electrospun strategies in topical products encompassing skincare and dermatological treatments.

As the potential applications of electrospinning in healthcare continue to be explored, along with advancements in industrial-scale solutions and the emergence of portable electrospinning devices, some researchers have explored electrospinning technology in topical products, including its application in skincare, such as facial masks, beauty patches, sunscreen, and dermatological treatments for conditions like atopic dermatitis, psoriasis, acne, skin cancer, etc. In this review, we first outline the fundamental principles of electrospinning and provide an overview of existing solutions for large-scale production and the components and functionalities of portable spinning devices. Based on the essential functionalities required for skincare products and the mechanisms and treatment methods for the aforementioned dermatological diseases, we summarize the potential advantages of electrospinning technology in these areas, including encapsulation, sustained release, large surface area, and biocompatibility, among others. Furthermore, considering the further commercialization and clinical development of electrospinning technology, we offer our insights on current challenges and future perspectives in these areas, including issues such as ingredients, functionality, residue concerns, environmental impact, and efficiency issues.

Matrikines in the skin: Origin, effects, and therapeutic potential.

The extracellular matrix (ECM) represents a complex multi-component environment that has a decisive influence on the biomechanical properties of tissues and organs. Depending on the tissue, ECM components are subject to a homeostasis of synthesis and degradation, a subtle interplay that is influenced by external factors and the intrinsic aging process and is often disturbed in pathologies. Upon proteolytic cleavage of ECM proteins, small bioactive peptides termed matrikines can be formed. These bioactive peptides play a crucial role in cell signaling and contribute to the dynamic regulation of both physiological and pathological processes such as tissue remodeling and repair as well as inflammatory responses. In the skin, matrikines exert an influence for instance on cell adhesion, migration, and proliferation as well as vasodilation, angiogenesis and protein expression. Due to their manifold functions, matrikines represent promising leads for developing new therapeutic options for the treatment of skin diseases. This review article gives a comprehensive overview on matrikines in the skin, including their origin in the dermal ECM, their biological effects and therapeutic potential for the treatment of skin pathologies such as melanoma, chronic wounds and inflammatory skin diseases or for their use in anti-aging cosmeceuticals.

Locally acting dermatology drug products: Pharmaco-analytic considerations for bioequivalence.

Bioequivalence determinations for locally acting dermatology drug products rely on assessing product sameness thru physicochemical composition and structure comparison, comparing the concentration of the active ingredient at the putative site of action, or comparing the clinical performance of the test (would-be generic) and reference products. Topical product action on cutaneous disease may be confounded by the action of excipients and are also subject to the inherent variability of how product may interact with the skin, including thermodynamic factors such as evaporation, spreadability, and interaction with the local environment such as heat and light and skin moisture.

Formulation and Characterization of Ethosomes for Transdermal Delivery of Prinsepia Utilis Rogle Seed Oil with Ameliorative Effects against UVB-Induced Skin Damage.

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization.

An Over-the-Counter Healing Ointment: Benefits in Dry Skin and Wound Healing.

BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures.  Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures.  Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects.  Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.

A Review of the Use of Intravenous Immunoglobulin Therapy in Dermatology.

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.