Drug Candidates for the Treatment of Skin Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 17840

Special Issue Editors


E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: skin diseases; psoriasis; NMSC; biomarker evaluation; clinical trial monitoring; pharmaceuticals; retinoids; infective diseases; drug efficacy evaluation; statistical analysis

E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: skin diseases; NMSC; psoriasis; melanoma; post-marketing drug surveillance; pharmaceuticals; retinoids; infective skin diseases; medical devices

Special Issue Information

Dear Colleagues,

This Special Issue aims to provide a comprehensive overview of the state of the art in innovative drugs for skin disease treatments.

Because it interfaces with the environment, skin plays a key role in protecting the body against pathogens and excessive water loss. Skin is also important for insulation, temperature regulation, sensation, synthesis of vitamin D, and the protection of vitamin B folates. Severely damaged skin, for exogenous or endogenous reasons, needs to be treated for the restoration of its functions.

Currently, there are several treatments for the treatment of skin diseases. In this Special Issue, the focus is on innovative treatments and on the correct comparison and/or evaluation of treatments, emphasizing the type of clinical trial or observational or prospective study used. Both in vitro and computational studies will be accepted.

The Special Issue will publish full research articles and systematic reviews that reflect current best practice in new drug candidates for the treatment of skin diseases.

Dr. Gaetana Costanza
Dr. Elena Campione
Guest Editors

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Keywords

  • skin diseases
  • psoriasis
  • NMSC
  • biomarker evaluation
  • clinical trial monitoring
  • pharmaceuticals
  • retinoids
  • infective diseases
  • drug efficacy evaluation
  • statistical analysis

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Published Papers (4 papers)

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Research

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15 pages, 3102 KiB  
Article
In Silico Characterization and Analysis of Clinically Significant Variants of Lipase-H (LIPH Gene) Protein Associated with Hypotrichosis
by Hamza Ali Khan, Muhammad Umair Asif, Muhammad Khurram Ijaz, Metab Alharbi, Yasir Ali, Faisal Ahmad, Ramsha Azhar, Sajjad Ahmad, Muhammad Irfan, Maryana Javed, Noorulain Naseer and Abdul Aziz
Pharmaceuticals 2023, 16(6), 803; https://doi.org/10.3390/ph16060803 - 29 May 2023
Viewed by 1893
Abstract
Hypotrichosis is an uncommon type of alopecia (hair loss) characterized by coarse scalp hair caused by the reduced or fully terminated activity of the Lipase-H (LIPH) enzyme. LIPH gene mutations contribute to the development of irregular or non-functional proteins. Because several cellular processes, [...] Read more.
Hypotrichosis is an uncommon type of alopecia (hair loss) characterized by coarse scalp hair caused by the reduced or fully terminated activity of the Lipase-H (LIPH) enzyme. LIPH gene mutations contribute to the development of irregular or non-functional proteins. Because several cellular processes, including cell maturation and proliferation, are inhibited when this enzyme is inactive, the hair follicles become structurally unreliable, undeveloped, and immature. This results in brittle hair, as well as altered hair shaft development and structure. Because of these nsSNPs, the protein’s structure and/or function may be altered. Given the difficulty in discovering functional SNPs in genes associated with disease, it is possible to assess potential functional SNPs before conducting broader population investigations. As a result, in our in silico analysis, we separated potentially hazardous nsSNPs of the LIPH gene from benign representatives using a variety of sequencing and architecture-based bioinformatics approaches. Using seven prediction algorithms, 9 out of a total of 215 nsSNPs were shown to be the most likely to cause harm. In order to distinguish between potentially harmful and benign nsSNPs of the LIPH gene, in our in silico investigation, we employed a range of sequence- and architecture-based bioinformatics techniques. Three nsSNPs (W108R, C246S, and H248N) were chosen as potentially harmful. The present findings will likely be helpful in future large population-based studies, as well as in drug discovery, particularly in the creation of personalized medicine, since this study provides an initial thorough investigation of the functional nsSNPs of LIPH. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Skin Diseases)
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13 pages, 3066 KiB  
Article
A Real-Life Study on the Use of Tildrakizumab in Psoriatic Patients
by Elena Campione, Sara Lambiase, Ruslana Gaeta Shumak, Marco Galluzzo, Caterina Lanna, Gaetana Costanza, Cristiana Borselli, Fabio Artosi, Terenzio Cosio, Lorenzo Tofani, Annunziata Dattola, Francesca Di Daniele and Luca Bianchi
Pharmaceuticals 2023, 16(4), 526; https://doi.org/10.3390/ph16040526 - 31 Mar 2023
Cited by 9 | Viewed by 2500
Abstract
Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based [...] Read more.
Tildrakizumab is a humanized IgG1κ monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. Descriptive and inferential statistical analyses were performed, in particular the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar Psoriasis Physician Global Assessment (PPPGA). These were assessed at baseline and after different timepoints (weeks) during the follow-up period. We described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. A total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). At week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Skin Diseases)
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21 pages, 4636 KiB  
Article
Anti-Alopecia Activity of Alkaloids Group from Noni Fruit against Dihydrotestosterone-Induced Male Rabbits and Its Molecular Mechanism: In Vivo and In Silico Studies
by Laila Susanti, Resmi Mustarichie, Eli Halimah, Dikdik Kurnia, Andi Setiawan and Yustinus Maladan
Pharmaceuticals 2022, 15(12), 1557; https://doi.org/10.3390/ph15121557 - 14 Dec 2022
Cited by 3 | Viewed by 4948
Abstract
Androgenic alopecia (AA) is a condition that most commonly affects adult men and is caused by an increase in the hormone dihydrotestosterone (DHT) in the hair follicles. Anti-alopecia drugs should be discovered for hair follicles to enter the anagen growth phase. Therefore, this [...] Read more.
Androgenic alopecia (AA) is a condition that most commonly affects adult men and is caused by an increase in the hormone dihydrotestosterone (DHT) in the hair follicles. Anti-alopecia drugs should be discovered for hair follicles to enter the anagen growth phase. Therefore, this study evaluated the hair growth-promoting activity of Noni fruit’s water, ethyl acetate, n-hexane fractions, and sub-fractions from the active fraction in the alopecia male white rabbit model. The Matias method was modified by inducing rabbits using DHT for 17 days, followed by topical application of Noni fruit solution for 21 days. Meanwhile, hair growth was evaluated by histological observation of the follicular density and the anagen/telogen (A/T) ratio in skin tissue. In the first stage, five groups of male white rabbits were studied to obtain the active fraction; DHT+Minoxidil as standard, DHT+vehicle (NaCMC 1%), DHT+FW, DHT+FEA, and DHT+FH. The FEA as the active fraction was followed by open-column chromatography separation (DCM:Methanol) with a gradient of 10% to produce sub-fractions. In the second stage, the six main sub-fraction groups of male rabbits studied were DHT+FEA-1 to DHT+FEA-6. The follicular density of groups FEA-3 was 78.00 ± 1.52 compared with 31.55 ± 1.64 and 80.12 ± 1.02 in the Vehicle and Minoxidil groups. Additionally, group FEA-3 showed large numbers of anagen follicles with an A/T ratio of 1.64/1 compared to the vehicle group of 1/1.50 and 1.39/1 for Minoxidil control. Group FEA-3 was identified by LC-MS/MS-QTOF, followed by molecular docking to the androgen receptor (PDB: 4K7A), causing alopecia. The results showed that three alkaloid compounds with skeleton piperazine and piperidine, namely (compounds 2 (−4.99 Kcal/mol), 3 (−4.60 Kcal/mol), and 4 (−4.57 Kcal/mol)) had a binding affinity similar to Minoxidil, with also has alkaloid skeleton piperidine–pyrimidine (−4.83 Kcal/mol). The dynamic behavior showed the stability of all androgen receptor compounds with good RMSD, SMSF, and SASA values after being studied with 100 ns molecular dynamics (MD) simulations. This study produced a common thread in discovering a class of alkaloid compounds as inhibitors of androgen receptors that cause alopecia. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Skin Diseases)
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Review

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11 pages, 1538 KiB  
Review
Insulin Resistance and Acne: The Role of Metformin as Alternative Therapy in Men
by Aikaterini Andreadi, Saverio Muscoli, Rojin Tajmir, Marco Meloni, Alessandro Minasi, Carolina Muscoli, Sara Ilari, Vincenzo Mollace, David Della Morte, Alfonso Bellia, Elena Campione, Nicola Di Daniele and Davide Lauro
Pharmaceuticals 2023, 16(1), 27; https://doi.org/10.3390/ph16010027 - 26 Dec 2022
Cited by 9 | Viewed by 7066
Abstract
The association between acne and insulin resistance has not been investigated as thoroughly in males as it has been in women, despite the fact that in adult men, acne prevalence has grown. On the face, sebaceous glands produce and secrete sebum, which lubricates [...] Read more.
The association between acne and insulin resistance has not been investigated as thoroughly in males as it has been in women, despite the fact that in adult men, acne prevalence has grown. On the face, sebaceous glands produce and secrete sebum, which lubricates the skin and protects it from friction. Metformin, an insulin-sensitizing medication, may modify the association between acne vulgaris and insulin resistance (IR). Individuals with IR, metabolic syndrome or with impaired glucose tolerance are sometimes treated ‘off label’ with Metformin. In these conditions, IR may be a leading factor in the pathogenesis of acne, and in men, Metformin treatment may reduce the Global Acne Grading System (GAGS) score by enhancing insulin sensitivity. However, additional clinical studies are required to corroborate these assumptions. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Skin Diseases)
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