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Keywords = anti-psoriatic drug

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26 pages, 685 KiB  
Article
Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data
by Diana Ana-Maria Nițescu, Horia Păunescu, Mihnea Costescu, Bogdan Nițescu, Laurențiu Coman, Ion Fulga and Oana Andreia Coman
Sci. Pharm. 2025, 93(3), 34; https://doi.org/10.3390/scipharm93030034 - 30 Jul 2025
Viewed by 261
Abstract
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment [...] Read more.
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article
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29 pages, 10452 KiB  
Article
Optimization of Anthralin Microemulgel Targeted Delivery for Psoriasis and Acne
by Samiksha Sakarkar, Swati Jagdale, Shrikant Dargude, Anuruddha Chabukswar, Shabana Urooj, Anusha Bilal and Hanan Abdullah Mengash
Molecules 2025, 30(12), 2629; https://doi.org/10.3390/molecules30122629 - 17 Jun 2025
Viewed by 448
Abstract
Background: Anthralin is known for its efficacy in treating psoriasis and acne, possessing poor solubility. Addressing these limitations, the present study endeavors to develop a microemulgel formulation of anthralin aimed at enhancing solubility. Method: The solubility study was performed in various solvents. An [...] Read more.
Background: Anthralin is known for its efficacy in treating psoriasis and acne, possessing poor solubility. Addressing these limitations, the present study endeavors to develop a microemulgel formulation of anthralin aimed at enhancing solubility. Method: The solubility study was performed in various solvents. An o/w (oil-in-water) emulsion was formed using the water titration method, which was optimized by statistical experimental design half-run CCD. The final optimized batch was evaluated for physicochemical and in vitro properties Result: The final optimized batch showed a particle size (PS) of 417 nm, −25.2 mV zeta potential (ZP) and pH 5.8, which remained stable upon centrifugation, heating–cooling and freeze–thawing cycle. Furthermore, microemulsion with Carbopol 943 5% w/v was selected as the gel base for the formation of microemulgel characterized by PS, ZP, pH, and viscosity of 230 nm, −50.6 mV, 6.9 and 14,200 cps, respectively, that ensured it a high enough stability. In silico molecular docking between ligand and protein provides the binding energies validating the interaction. Hence, the in silico study was performed for psoriasis and P. acne proteins. An in vitro antibacterial activity study on Propionibacterium revealed a significant efficiency of the formulation and MTT assay using L929 cell line in the presence of the drug-loaded microemulgel indicated an inhibition of growth proving that formulation has anti-psoriatic activity. Conclusions: Combination therapy with Clindamycin might improve efficacy while reducing antibiotic resistance risks. Full article
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15 pages, 617 KiB  
Article
Italian Multicenter Real-World Study on the Twelve-Month Effectiveness, Safety, and Retention Rate of Guselkumab in Psoriatic Arthritis Patients
by Fabiola Atzeni, Cinzia Rotondo, Cesare Siragusano, Addolorata Corrado, Alberto Cauli, Roberto Caporali, Maria Sole Chimenti, Fabrizio Conti, Valentina Picerno, Elisa Gremese, Federica Camarda, Serena Guiducci, Roberta Ramonda, Luca Idolazzi, Angelo Semeraro, Marco Sebastiani, Giovanni Lapadula, Gianfranco Ferraccioli and Florenzo Iannone
J. Clin. Med. 2025, 14(12), 4111; https://doi.org/10.3390/jcm14124111 - 10 Jun 2025
Viewed by 734
Abstract
Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with [...] Read more.
Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article
(This article belongs to the Special Issue Targeted Treatment in Chronic Inflammatory Arthritis)
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26 pages, 1152 KiB  
Review
Juvenile Spondyloarthropathies: Diagnostic and Therapeutic Advances—A Narrative Review
by Călin Lazăr, Mirela Crișan, Oana-Iulia Man, Lucia Maria Sur, Gabriel Samașca and Alexandru Cristian Bolunduț
J. Clin. Med. 2025, 14(9), 3166; https://doi.org/10.3390/jcm14093166 - 3 May 2025
Viewed by 750
Abstract
Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According [...] Read more.
Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According to the International League of Associations for Rheumatology criteria, JSpAs include several specific forms: enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Despite established classifications, the terms and definitions surrounding these conditions can often lead to confusion among healthcare professionals. This ambiguity underscores the need for a standardized approach to nosological classification. The clinical presentation of JSpAs can be multifaceted, encompassing both articular and extra-articular manifestations. Articular symptoms may include enthesitis and varying forms of arthritis, while extra-articular involvement can range from uveitis to gastrointestinal, cardiovascular, pulmonary, neurological, and renal complications. These diverse manifestations highlight the systemic nature of the disease and the importance of a holistic approach to diagnosis and treatment. While laboratory tests for SpAs are often non-specific, imaging modalities such as musculoskeletal ultrasound and magnetic resonance imaging play a crucial role in the early detection of inflammatory lesions. These imaging techniques can provide valuable insights into disease progression and aid in the formulation of appropriate treatment plans. Current treatment guidelines advocate for a “stepwise” approach to therapy, beginning with nonsteroidal anti-inflammatory drugs and progressing to glucocorticoids, disease-modifying antirheumatic drugs, and biological agents, particularly anti-tumor necrosis factor alpha agents. The primary objective of treatment is to achieve clinical remission or, at a minimum, to attain low disease activity. Regular monitoring of disease activity is imperative; however, the lack of validated assessment tools for the pediatric population remains a significant challenge. JSpAs pose unique challenges in terms of diagnosis and management due to their diverse manifestations and the complexities of their classification. Ongoing research and clinical efforts are essential to refine our understanding of these conditions, improve treatment outcomes, and enhance quality of life for affected children and their families. Effective management hinges on early detection, individualized treatment plans, and continuous monitoring, ensuring that patients receive the most appropriate care tailored to their specific needs. Full article
(This article belongs to the Section Clinical Pediatrics)
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22 pages, 4622 KiB  
Article
An Inhaled Nanoemulsion Encapsulating a Herbal Drug for Non-Small Cell Lung Cancer (NSCLC) Treatment
by Mural Quadros, Mimansa Goyal, Gautam Chauhan, Dnyandev Gadhave and Vivek Gupta
Pharmaceutics 2025, 17(5), 540; https://doi.org/10.3390/pharmaceutics17050540 - 22 Apr 2025
Viewed by 955
Abstract
Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to [...] Read more.
Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). Methods: The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. Results: The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of −15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC50 (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. Conclusions: The inhalable NE-Cela formulation improved Cela’s physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment. Full article
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28 pages, 9610 KiB  
Article
Development and Evaluation of Hydrogel-Based Sulfasalazine-Loaded Nanosponges for Enhanced Topical Psoriasis Therapy
by Sunil Kumar, Anroop B. Nair, Varsha Kadian, Pooja Dalal, Babu Lal Jangir, Bandar Aldhubiab, Rashed M. Almuqbil, Ahmed S. Alnaim, Nouf Alwadei and Rekha Rao
Pharmaceuticals 2025, 18(3), 391; https://doi.org/10.3390/ph18030391 - 10 Mar 2025
Cited by 1 | Viewed by 1190
Abstract
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared [...] Read more.
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared by the melt polymerization method and evaluated for physiochemical characteristics, drug release, and cytocompatibility. The selected nanosponges (SLZ-NS4) were transformed to hydrogel and further evaluated for rheology, texture, safety, skin permeability, and in vivo for anti-psoriatic effect in mouse tail and imiquimod-induced psoriasis-like inflammation models in mice. Results: Physiochemical data confirms nanoscale architecture, drug inclusion in nanosponges, crystalline structure, and formulation stability. The release profile of SLZ-NS4 revealed sustained release behavior (22.98 ± 2.24% in 3 h). Cytotoxicity assays indicated negligible toxicity against THP1 cells, resulting in higher viability of cells than pure SLZ (p < 0.05). The HET-CAM assay confirmed the safety, while confocal laser scanning microscopy demonstrated deeper skin permeation of SLZ. In the mouse tail model, a remarkable decline in relative epidermal thickness, potential improvement in percent orthokeratosis, and drug activity with respect to control was observed in animals treated with SLZ-NS4 hydrogel. The efficiency of the developed SLZ-NS4-loaded hydrogel in treating psoriasis was confirmed by the decline in PASI score (81.68 ± 3.61 and 84.86 ± 5.74 with 1 and 2% w/v of SLZ-NS-HG). Histopathological analysis and assessment of oxidative stress markers revealed the profound anti-psoriatic potential of the fabricated SLZ-NS4 hydrogel. Conclusions: These findings highlight the profound potential of the developed delivery system as an effective topical therapy for psoriasis. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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15 pages, 1056 KiB  
Article
Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial
by Jelena Petković-Dabić, Ivana Binić, Bojana Carić, Ljiljana Božić, Sanja Umičević-Šipka, Nataša Bednarčuk, Saša Dabić, Mirna Šitum, Snježana Popović-Pejičić, Miloš P. Stojiljković and Ranko Škrbić
Biomolecules 2025, 15(1), 46; https://doi.org/10.3390/biom15010046 - 1 Jan 2025
Cited by 8 | Viewed by 3670
Abstract
Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory [...] Read more.
Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM. Full article
(This article belongs to the Section Biological Factors)
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23 pages, 8373 KiB  
Article
Cyclodextrin-Nanosponge-Loaded Cyclo-Oxygenase-2 Inhibitor-Based Topical Gel for Treatment of Psoriatic Arthritis: Formulation Design, Development, and In vitro Evaluations
by Umme Hani, Sharanya Paramshetti, Mohit Angolkar, Wajan Khalid Alqathanin, Reema Saeed Alghaseb, Saja Mohammed Al Asmari, Alhanouf A. Alsaab, Farhat Fatima, Riyaz Ali M. Osmani and Ravi Gundawar
Pharmaceuticals 2024, 17(12), 1598; https://doi.org/10.3390/ph17121598 - 27 Nov 2024
Cited by 3 | Viewed by 1699
Abstract
Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have [...] Read more.
Background: Psoriatic arthritis (PsA), a chronic inflammatory disease, mainly affects the joints, with approximately 30% of psoriasis patients eventually developing PsA. Characterized by both innate and adaptive immune responses, PsA poses significant challenges for effective treatment. Recent advances in drug delivery systems have sparked interest in developing novel formulations to improve therapeutic outcomes. The current research focuses on the development and evaluation of a nanosponge-loaded, cyclo-oxygenase-2 (COX-2) inhibitor-based topical gel for the treatment of PsA. Methods: Nanosponges (NSs) were prepared by using beta-cyclodextrin as a polymer and dimethyl carbonate (DMC) as a crosslinker by melting, and gels were prepared by employing carbopol and badam gum as polymers. Results: Solubility studies confirmed that the prepared nanosponges were highly soluble. FT-IR studies confirmed the formation of hydrogen bonds between lumiracoxib and beta-cyclodextrin. SEM confirmed that the prepared formulations were roughly spherical and porous in nature. The average particle size was 190.5 ± 0.02 nm, with a zeta potential of −18.9 mv. XRD studies showed that the crystallinity of lumiracoxib decreased after encapsulation, which helped to increase its solubility. The optimized nanosponges (NS2) were incorporated in an optimized gel (FG10) to formulate a nanosponge-loaded topical gel. The optimized gel formulation exhibited a homogeneous consistency, with a pH of 6.8 and a viscosity of 1.15 PaS, indicating its suitability for topical application and stability. The in vitro diffusion studies for the topical gel showed drug release of 82.32% in 24 h. The optimized formulation demonstrated significant antipsoriatic activity, as confirmed through cytotoxicity studies conducted on HaCaT cells. Conclusions: On the basis of the findings, it can be concluded that the prepared nanosponge-loaded topical gel formulation presents a promising solution for the effective management of PsA, offering enhanced drug solubility, sustained release, and improved therapeutic potential. Full article
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8 pages, 810 KiB  
Article
Drug Survival and Clinical Course of Patients with Cancer Treated with Biologic Therapy for Psoriasis
by Nicole Macagno, Luca Mastorino, Michela Ortoncelli, Silvia Borriello, Chiara Astrua, Anna Verrone, Elena Stroppiana, Paolo Dapavo, Niccolò Siliquini, Simone Ribero and Pietro Quaglino
J. Clin. Med. 2024, 13(21), 6546; https://doi.org/10.3390/jcm13216546 - 31 Oct 2024
Cited by 4 | Viewed by 1648
Abstract
Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special [...] Read more.
Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions: IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events. Full article
(This article belongs to the Special Issue Targeted Treatment of Skin Inflammation)
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2 pages, 132 KiB  
Abstract
Towards Skin Longevity: The Development of a Novel Plant-Based Combination with a Potent Stimulation of Collagen I Synthesis In Vitro
by Viktor Filatov and Elizaveta Patronova
Proceedings 2024, 103(1), 65; https://doi.org/10.3390/proceedings2024103065 - 12 Apr 2024
Viewed by 769
Abstract
Human skin is constantly exposed to various endogenous and exogenous factors, including UV radiation and vitamin deficiency, which can influence the earlier appearance of visible wrinkles and decrease skin firmness and elasticity. This process is related to decreased collagen I synthesis in the [...] Read more.
Human skin is constantly exposed to various endogenous and exogenous factors, including UV radiation and vitamin deficiency, which can influence the earlier appearance of visible wrinkles and decrease skin firmness and elasticity. This process is related to decreased collagen I synthesis in the dermis. However, the use of retinol derivatives, synthetic molecules, and growth factors is associated with significant adverse effects, low bioavailability, and instability in dermatological products. Thus, our research was focused on the investigation of a novel plant-based combination for the stimulation of collagen I synthesis in deep skin layers and the prevention of accelerated skin ageing. Aloe barbadensis leaf extract, trimethylglycine, and panthenol were chosen as potential candidates using in silico modelling. A Way2Drug tool predicted anti-inflammatory, anti-psoriatic, and antioxidant activities beneficial for the prophylaxis of skin ageing. An in vitro study was conducted to determine collagen I synthesis in skin fibroblasts in the presence of single substances and their composition using a colorimetric analysis. It was revealed that the combination of Aloe barbadensis leaf extract, trimethylglycine, and panthenol in a specific mass ratio of 2:4:1 and at a concentration of 0.5% significantly increased the amount of collagen I in the skin fibroblasts by up to +18% within 24 h (p < 0.001). This effect was comparable to that of TGF-β1 (10 ng/mL), with a 37% collagen I increase (p < 0.001). The single compounds and the combination of Aloe barbadensis leaf extract and trimethylglycine showed a negative effect on collagen I synthesis, with an unpredictable decrease in this protein in fibroblasts. The combination of the compounds made it possible to achieve a synergistic effect, boosting the natural rejuvenation process in fibroblasts. Overall, the results indicate that the developed plant-based composition in the specific mass ratio and concentration given above could increase collagen I synthesis and can be considered a promising substance for dermatological products with reverse anti-ageing effects. Full article
(This article belongs to the Proceedings of The 3rd International Electronic Conference on Biomolecules)
44 pages, 2418 KiB  
Review
Recent Approaches for the Topical Treatment of Psoriasis Using Nanoparticles
by Krisztina Bodnár, Pálma Fehér, Zoltán Ujhelyi, Ildikó Bácskay and Liza Józsa
Pharmaceutics 2024, 16(4), 449; https://doi.org/10.3390/pharmaceutics16040449 - 25 Mar 2024
Cited by 26 | Viewed by 9737
Abstract
Psoriasis (PSO) is a chronic autoimmune skin condition characterized by the rapid and excessive growth of skin cells, which leads to the formation of thick, red, and scaly patches on the surface of the skin. These patches can be itchy and painful, and [...] Read more.
Psoriasis (PSO) is a chronic autoimmune skin condition characterized by the rapid and excessive growth of skin cells, which leads to the formation of thick, red, and scaly patches on the surface of the skin. These patches can be itchy and painful, and they may cause discomfort for patients affected by this condition. Therapies for psoriasis aim to alleviate symptoms, reduce inflammation, and slow down the excessive skin cell growth. Conventional topical treatment options are non-specific, have low efficacy and are associated with adverse effects, which is why researchers are investigating different delivery mechanisms. A novel approach to drug delivery using nanoparticles (NPs) shows promise in reducing toxicity and improving therapeutic efficacy. The unique properties of NPs, such as their small size and large surface area, make them attractive for targeted drug delivery, enhanced drug stability, and controlled release. In the context of PSO, NPs can be designed to deliver active ingredients with anti-inflammatory effect, immunosuppressants, or other therapeutic compounds directly to affected skin areas. These novel formulations offer improved access to the epidermis and facilitate better absorption, thus enhancing the therapeutic efficacy of conventional anti-psoriatic drugs. NPs increase the surface-to-volume ratio, resulting in enhanced penetration through the skin, including intracellular, intercellular, and trans-appendage routes. The present review aims to discuss the latest approaches for the topical therapy of PSO using NPs. It is intended to summarize the results of the in vitro and in vivo examinations carried out in the last few years regarding the effectiveness and safety of nanoparticles. Full article
(This article belongs to the Special Issue Nanoparticles for Local Drug Delivery)
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13 pages, 1927 KiB  
Article
PIM Kinases as Potential Biomarkers and Therapeutic Targets in Inflammatory Arthritides
by Elisa Assirelli, Jacopo Ciaffi, Valentina Scorcu, Susanna Naldi, Veronica Brusi, Luana Mancarella, Lucia Lisi, Federica Pignatti, Francesco Ursini and Simona Neri
Int. J. Mol. Sci. 2024, 25(6), 3123; https://doi.org/10.3390/ijms25063123 - 8 Mar 2024
Cited by 3 | Viewed by 2132
Abstract
The Proviral Integration site for the Moloney murine leukemia virus (PIM)-1 kinase and its family members (PIM-2 and PIM-3) regulate several cellular functions including survival, proliferation, and apoptosis. Recent studies showed their involvement in the pathogenesis of rheumatoid arthritis RA, while no studies [...] Read more.
The Proviral Integration site for the Moloney murine leukemia virus (PIM)-1 kinase and its family members (PIM-2 and PIM-3) regulate several cellular functions including survival, proliferation, and apoptosis. Recent studies showed their involvement in the pathogenesis of rheumatoid arthritis RA, while no studies are available on psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). The main objective of this study is to assess the expression of PIM kinases in inflammatory arthritides, their correlation with proinflammatory cytokines, and their variation after treatment with biologic disease-modifying anti-rheumatic drugs or JAK inhibitors. We evaluated PIM-1, -2, and -3 expression at the gene and protein level, respectively, in the peripheral blood mononuclear cells and serum of patients with RA, PsA, axSpA, and healthy individuals (CTR). All the samples showed expression of PIM-1, -2, and -3 kinases both at the gene and protein level. PIM-1 was the most expressed protein, PIM-3 the least. PIM kinase levels differed between controls and disease groups, with reduced PIM-1 protein and increased PIM-3 protein in all disease samples compared to controls. No difference was found in the expression of these molecules between the three different pathologies. PIM levels were not modified after 6 months of therapy. In conclusion, our preliminary data suggest a deregulation of the PIM pathway in inflammatory arthritides. In-depth studies on the role of PIM kinases in this field are warranted. Full article
(This article belongs to the Special Issue Molecular and Therapeutic Research in Rheumatoid Arthritis)
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24 pages, 4036 KiB  
Article
Nanophytosomal Gel of Heydotis corymbosa (L.) Extract against Psoriasis: Characterisation, In Vitro and In Vivo Biological Activity
by Neelam Singh, Ayaz Mukarram Shaikh, Puneet Gupta, Béla Kovács, Mohammed F. Abuzinadah, Aftab Ahmad, Radha Goel, Swapnil Singh and Chaitanya Vinayak
Pharmaceuticals 2024, 17(2), 213; https://doi.org/10.3390/ph17020213 - 6 Feb 2024
Cited by 5 | Viewed by 3037
Abstract
The current study was conducted to examine the possible advantages of Heydotis corymbosa (L.) Lam. extract nanogel as a perspective for enhanced permeation and extended skin deposition in psoriasis-like dermatitis. Optimised nanophytosomes (NPs) were embedded in a pluronic gel base to obtain nanogel [...] Read more.
The current study was conducted to examine the possible advantages of Heydotis corymbosa (L.) Lam. extract nanogel as a perspective for enhanced permeation and extended skin deposition in psoriasis-like dermatitis. Optimised nanophytosomes (NPs) were embedded in a pluronic gel base to obtain nanogel and tested ex vivo (skin penetration and dermatokinetics) and in vivo. The optimised NPs had a spherical form and entrapment efficiency of 73.05 ± 1.45% with a nanosized and zeta potential of 86.11 nm and −10.40 mV, respectively. Structural evaluations confirmed encapsulation of the drug in the NPs. Topical administration of prepared nanogel to a rat model of psoriasis-like dermatitis revealed its specific in vivo anti-psoriatic efficacy in terms of drug activity compared to the control and other formulations. Nanogel had improved skin integrity and downregulation of inflammatory cytokines. These findings suggest that developed phytoconstituent-based nanogel has the potential to alleviate psoriasis-like dermatitis with better skin retention and effectiveness. Full article
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24 pages, 9087 KiB  
Article
Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery
by Natália Andrýsková, Jozef Motyčka, Melánia Babincová, Peter Babinec and Mária Šimaljaková
Appl. Sci. 2024, 14(3), 1094; https://doi.org/10.3390/app14031094 - 27 Jan 2024
Cited by 3 | Viewed by 2054
Abstract
Psoriasis is a chronic autoimmune skin disorder characterized by the rapid overproduction of skin cells, resulting in the formation of red, inflamed, and scaly patches or plaques on the skin. Dithranol, also known as anthralin, is a very effective topical medication used in [...] Read more.
Psoriasis is a chronic autoimmune skin disorder characterized by the rapid overproduction of skin cells, resulting in the formation of red, inflamed, and scaly patches or plaques on the skin. Dithranol, also known as anthralin, is a very effective topical medication used in the treatment of psoriasis, with several shortcomings like photo-instability; staining skin, clothing, and bedding; and causing skin irritation. Antiproliferative dithranol is frequently used in combination therapy with keratolytic salicylic acid. We have therefore proposed a novel topical antipsoriatic prodrug comprising dithranol and salicylic acid joined together with an ester bond, specifically 8-hydroxy-9-oxo-9,10-dihydroanthracen-1-yl-2-hydroxybenzoate. An ester bond is cleavable by endogenous esterase hydrolyzing this bond and releasing dithranol and salicylic acid in a 1:1 stoichiometric ratio. We performed an exhaustive theoretical analysis of this molecule using the reliable computational methods of quantum chemistry and ADME in silico studies to investigate its biological and pharmacokinetic activities. We found its molecular structure, vibrational spectra, molecular orbitals, MEP (molecular electric potential), UV-VIS spectra, and TDOS (total density of states), and we performed an RDG (reduced density gradient) analysis. The obtained results may be useful for the understanding of its properties, which may assist in the synthesis and further experimental study of this possible antipsoriatic dual-action prodrug with reduced adverse effects and enhanced therapeutic efficacy. Full article
(This article belongs to the Special Issue Young Investigators in Advanced Drug Delivery)
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15 pages, 3465 KiB  
Article
Enhancement of Curcumin’s Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel
by Km Reena, Saurabh Mittal, Mohammad Faizan, Iram Jahan, Yasir Rahman, Rahmuddin Khan, Lalit Singh, Abdulsalam Alhalmi, Omar M. Noman and Ahmad Alahdab
Gels 2023, 9(12), 973; https://doi.org/10.3390/gels9120973 - 13 Dec 2023
Cited by 6 | Viewed by 3706
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as [...] Read more.
Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel’s 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel’s potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis. Full article
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