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22 pages, 2508 KiB

Open AccessArticle

A New Approach to Atopic Dermatitis Control with Low-Concentration Propolis-Loaded Cold Cream

by Bianca Aparecida Martin, Camila Nunes Lemos, Luciana Facco Dalmolin, Caroline Arruda, Íris Sperchi Camilo Brait, Maurílio de Souza Cazarim, Estael Luzia Coelho da Cruz-Cazarim, Paula Carolina Pires Bueno, Maurílio Polizello Júnior, Leonardo Régis Leira Pereira, Renata Nahas Cardili and Renata Fonseca Vianna Lopez

Pharmaceutics 2021, 13(9), 1346; https://doi.org/10.3390/pharmaceutics13091346 - 27 Aug 2021

Cited by 6 | Viewed by 2980

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is difficult to treat. Traditional cold cream, a water-in-oil emulsion made from beeswax, is used to alleviate AD symptoms in clinical practice, although its effectiveness has not been scientifically proven. The addition of [...] Read more.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is difficult to treat. Traditional cold cream, a water-in-oil emulsion made from beeswax, is used to alleviate AD symptoms in clinical practice, although its effectiveness has not been scientifically proven. The addition of propolis has the potential to impart anti-inflammatory properties to cold cream. However, in high concentrations, propolis can trigger allergic reactions. Thus, the objective of this work was to develop a cold cream formulation based on purified beeswax containing the same amount of green propolis present in raw beeswax. The impact of adding this low propolis concentration to cold cream on AD control was evaluated in patients compared to cold cream without added propolis (CBlank). Raw beeswax was chemically characterized to define the propolis concentration added to the propolis-loaded cold cream (CPropolis). The creams were characterized as to their physicochemical, mechanical, and rheological characteristics. The effect of CPropolis and CBlank on the quality of life, disease severity, and skin hydration of patients with AD was evaluated in a triple-blind randomized preclinical study. Concentrations of 34 to 120 ng/mL of green propolis extract reduced TNF-α levels in LPS-stimulated macrophage culture. The addition of propolis to cold cream did not change the cream’s rheological, mechanical, or bioadhesive properties. The preclinical study suggested that both creams improved the patient’s quality of life. Furthermore, the use of CPropolis decreased the disease severity compared to CBlank. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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19 pages, 3153 KiB

Open AccessArticle

Prevention and Treatment of Fungal Skin Infections Using Cationic Polymeric Films

by Fritz Ka-Ho Ho, Albert Bolhuis and M. Begoña Delgado-Charro

Pharmaceutics 2021, 13(8), 1161; https://doi.org/10.3390/pharmaceutics13081161 - 28 Jul 2021

Cited by 1 | Viewed by 2367

Abstract

Dermatophytosis is a fungal infection of skin, nails and hair. Treatments can be long and infections are often recurrent, and novel treatments are desirable. Here we tested the use of polymeric films that can be sprayed on the skin for the prevention and [...] Read more.

Dermatophytosis is a fungal infection of skin, nails and hair. Treatments can be long and infections are often recurrent, and novel treatments are desirable. Here we tested the use of polymeric films that can be sprayed on the skin for the prevention and treatment of dermatophytosis. The two polymers selected were ABIL T Quat 60 and Eudragit E100, which were tested ex vivo using a porcine skin model, and in vitro using microbiological and microscopy techniques. Acceptability of the polymeric films was tested on the skin of healthy volunteers. The results showed that ABIL and Eudragit films prevented and treated fungal skin infections. Whilst polymer films may provide a physical barrier that prevents fungal colonization, it was shown that both polymers are active antifungals ex vivo and in vitro and have intrinsic antifungal activity. For ABIL, we also established that this polymer binds essential nutrients such as metal ions and sugars, thereby restricting the growth of fungi. When applied to healthy subjects’ skin, the polymeric films neither modified the skin color nor increased trans-epidermal water loss, suggesting a low potential for skin irritation, and the approach was generally found to be acceptable for use by the volunteers. In conclusion, we developed a novel strategy for the potential prevention and treatment of dermatophytosis. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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20 pages, 3999 KiB

Open AccessArticle

The Stimulating Effect of Rosmarinic Acid and Extracts from Rosemary and Lemon Balm on Collagen Type I Biosynthesis in Osteogenesis Imperfecta Type I Skin Fibroblasts

by Joanna Sutkowska, Natalia Hupert, Katarzyna Gawron, Jakub W. Strawa, Michał Tomczyk, Antonella Forlino and Anna Galicka

Pharmaceutics 2021, 13(7), 938; https://doi.org/10.3390/pharmaceutics13070938 - 23 Jun 2021

Cited by 8 | Viewed by 3667

Abstract

Rosemary extract (RE) and lemon balm extract (LBE) attract particular attention of pharmacists due to their high therapeutic potential. Osteogenesis imperfecta (OI) type I is a heritable disease caused by mutations in type I collagen and characterized by its reduced amount. The aim [...] Read more.

Rosemary extract (RE) and lemon balm extract (LBE) attract particular attention of pharmacists due to their high therapeutic potential. Osteogenesis imperfecta (OI) type I is a heritable disease caused by mutations in type I collagen and characterized by its reduced amount. The aim of the study was to evaluate the effect of the extracts and rosmarinic acid (RA) on collagen type I level in OI skin fibroblasts. Phytochemical analysis of RE and LBE was carried out by liquid chromatography–photodiode array detection–mass spectrometry. The expression of collagen type I at transcript and protein levels was analyzed by qPCR, ELISA, SDS-urea PAGE, and Western blot. In OI patient’s fibroblasts the exposure to the extracts (0.1–100 µg/mL) and RA (0.1–100 µM) significantly increased collagen type I and the best results were obtained with 0.1–10 µM RA and 0.1–10 µg/mL of the extracts. LBE showed a greater stimulating effect than RE, likely due to a higher RA content. Moreover, collagen type III expression and matrix metalloproteinase (MMP-1, -2, -9) activity remained unchanged or decreased. The obtained data support the clinical potential of RA-rich extracts and RA itself in modulating the quantitative defect of type I collagen in type I OI. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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36 pages, 16028 KiB

Open AccessArticle

Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial

by Sara Ud-Din, Traci A. Wilgus, Douglas D. McGeorge and Ardeshir Bayat

Pharmaceutics 2021, 13(4), 510; https://doi.org/10.3390/pharmaceutics13040510 - 08 Apr 2021

Cited by 14 | Viewed by 2782

Abstract

The concept of pre-emptive priming of skin pre-surgery offers a novel approach in optimizing cutaneous scarring outcome. We previously showed an anti-scarring topical (epigallocatechin-3-gallate (EGCG)) is effective in improving skin scarring when applied post-surgery. The objective was to deliver an active compound at [...] Read more.

The concept of pre-emptive priming of skin pre-surgery offers a novel approach in optimizing cutaneous scarring outcome. We previously showed an anti-scarring topical (epigallocatechin-3-gallate (EGCG)) is effective in improving skin scarring when applied post-surgery. The objective was to deliver an active compound at the optimal time in order to maximize its impact and improve cutaneous scarring. Therefore, pre-emptive application of anti-scarring topical pre-surgery compared with post-surgery can potentially be superior on scarring outcome. This double-blinded randomized placebo-controlled trial compares the effects of pre-emptive priming of skin with an anti-scarring topical pre-surgery versus post-surgery. Healthy volunteers (n = 40) were split into 4-groups; each undergoing different modes of application versus placebo: Group-1 = priming (7Days) pre-injury, Group-2 = priming (3D) pre-injury, Group-3 = immediate (0D) day-of-injury, Group-4 = delayed application (14D) post-injury. Excisional skin-biopsies in upper-arms were evaluated weekly with multiple quantitative devices over 8-weeks. Histological, immunohistochemical, mRNA sequencing and QRT-PCR studies were performed on tissue-biopsies. EGCG reduced mast cells at weeks-4 and 8 by gene and protein analyses (p < 0.01). Group 1 was superior to other groups (p < 0.01) in both clinical (blood flow) and laboratory parameters (elastin and immune marker expression). Additionally, there was down-regulation of angiogenic-markers by mRNA-sequencing and of CD31 and VEGF-A at weeks-4 and 8 (p < 0.01) by immunohistochemistry and at week-4 (p < 0.05) by QRT-PCR. EGCG increased antioxidant levels (HO-1) at week-4 (p < 0.01) plus elastin at week-8 (p < 0.01). In conclusion, pre-emptive priming of skin pre-injury has significant beneficial effects on surgically induced skin scarring shown by reducing mast cells, blood flow and angiogenesis plus increasing elastin content. This clinical trial was registered with ISRCTN (ISRCTN70155584). Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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Review

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32 pages, 3225 KiB

Open AccessReview

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

by María Guadalupe Frías-De-León, Rigoberto Hernández-Castro, Esther Conde-Cuevas, Itzel H. García-Coronel, Víctor Alfonso Vázquez-Aceituno, Marvin A. Soriano-Ursúa, Eunice D. Farfán-García, Esther Ocharán-Hernández, Carmen Rodríguez-Cerdeira, Roberto Arenas, Maura Robledo-Cayetano, Tito Ramírez-Lozada, Patricia Meza-Meneses, Rodolfo Pinto-Almazán and Erick Martínez-Herrera

Pharmaceutics 2021, 13(10), 1529; https://doi.org/10.3390/pharmaceutics13101529 - 22 Sep 2021

Cited by 20 | Viewed by 4330

Abstract

In recent years, a progressive increase in the incidence of invasive fungal infections (IFIs) caused by Candida glabrata has been observed. The objective of this literature review was to study the epidemiology, drug resistance, and virulence factors associated with the C. glabrata complex. [...] Read more.

In recent years, a progressive increase in the incidence of invasive fungal infections (IFIs) caused by Candida glabrata has been observed. The objective of this literature review was to study the epidemiology, drug resistance, and virulence factors associated with the C. glabrata complex. For this purpose, a systematic review (January 2001–February 2021) was conducted on the PubMed, Scielo, and Cochrane search engines with the following terms: “C. glabrata complex (C. glabrata sensu stricto, C. nivariensis, C. bracarensis)” associated with “pathogenicity” or “epidemiology” or “antibiotics resistance” or “virulence factors” with language restrictions of English and Spanish. One hundred and ninety-nine articles were found during the search. Various mechanisms of drug resistance to azoles, polyenes, and echinocandins were found for the C. glabrata complex, depending on the geographical region. Among the mechanisms found are the overexpression of drug transporters, gene mutations that alter thermotolerance, the generation of hypervirulence due to increased adhesion factors, and modifications in vital enzymes that produce cell wall proteins that prevent the activity of drugs designed for its inhibition. In addition, it was observed that the C. glabrata complex has virulence factors such as the production of proteases, phospholipases, and hemolysins, and the formation of biofilms that allows the complex to evade the host immune response and generate fungal resistance. Because of this, the C. glabrata complex possesses a perfect pathogenetic combination for the invasion of the immunocompromised host. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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14 pages, 1742 KiB

Open AccessReview

Topical L-Ascorbic Acid Formulation for a Better Management of Non-Melanoma Skin Cancer: Perspective for Treatment Strategies

by Pier Cesare Capponi, Domenico Murri and Carmine Pernice

Pharmaceutics 2021, 13(8), 1201; https://doi.org/10.3390/pharmaceutics13081201 - 04 Aug 2021

Cited by 5 | Viewed by 2463

Abstract

L-ascorbic acid, is a well-known molecule, sometimes used as antioxidant for skin care. Nonetheless, few studies have taken in account its utility as topical treatment for non-melanoma skin vancer. Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma and is widespread [...] Read more.

L-ascorbic acid, is a well-known molecule, sometimes used as antioxidant for skin care. Nonetheless, few studies have taken in account its utility as topical treatment for non-melanoma skin vancer. Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma and is widespread worldwide with an increasing incidence. The purpose of this paper is to analyze the characteristics of L-ascorbic acid topical formulation, its percutaneous absorption and biochemical mechanism, focusing on its anti-cancer properties. In particular, it will be described how the pH and the concentration of the formulation are able to influence its distribution in the skin and tissues. We will report, the current knowledge on the pharmacokinetic aspects of L-ascorbic acid that allows us to reconsider it in the light of its ability to act as a prodrug and as an anticancer agent. Lastly, a short review with the aim to find any evidence of a possible clinical use of L-ascorbic acid for the treatment of non-melanoma skin cancer was made. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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24 pages, 2952 KiB

Open AccessReview

Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis

by Jen-Chih Tseng, Yung-Chi Chang, Chun-Ming Huang, Li-Chung Hsu and Tsung-Hsien Chuang

Pharmaceutics 2021, 13(7), 1064; https://doi.org/10.3390/pharmaceutics13071064 - 11 Jul 2021

Cited by 14 | Viewed by 4336

Abstract

Psoriasis, a complex inflammatory autoimmune skin disorder that affects 2–3% of the global population, is thought to be genetically predetermined and induced by environmental and immunological factors. In the past decades, basic and clinical studies have significantly expanded knowledge on the molecular, cellular, [...] Read more.

Psoriasis, a complex inflammatory autoimmune skin disorder that affects 2–3% of the global population, is thought to be genetically predetermined and induced by environmental and immunological factors. In the past decades, basic and clinical studies have significantly expanded knowledge on the molecular, cellular, and immunological mechanisms underlying the pathogenesis of psoriasis. Based on these pathogenic mechanisms, the current disease model emphasizes the role of aberrant Th1 and Th17 responses. Th1 and Th17 immune responses are regulated by a complex network of different cytokines, including TNF-α, IL-17, and IL-23; signal transduction pathways downstream to the cytokine receptors; and various activated transcription factors, including NF-κB, interferon regulatory factors (IRFs), and signal transducer and activator of transcriptions (STATs). The biologics developed to specifically target the cytokines have achieved a better efficacy and safety for the systemic management of psoriasis compared with traditional treatments. Nevertheless, the current therapeutics can only alleviate the symptoms; there is still no cure for psoriasis. Therefore, the development of more effective, safe, and affordable therapeutics for psoriasis is important. In this review, we discussed the current trend of therapeutic development for psoriasis based on the recent discoveries in the immune modulation of the inflammatory response in psoriasis. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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12 pages, 1858 KiB

Open AccessReview

Developing a JAK Inhibitor for Targeted Local Delivery: Ruxolitinib Cream

by Paul Smith, Wenqing Yao, Stacey Shepard, Maryanne Covington, Jim Lee, Jennifer Lofland, Ahmad Naim, Trupti Sheth, Bhavnish Parikh and Swamy Yeleswaram

Pharmaceutics 2021, 13(7), 1044; https://doi.org/10.3390/pharmaceutics13071044 - 08 Jul 2021

Cited by 15 | Viewed by 5419

Abstract

Named after the two-faced Roman god of doorways, Janus kinases (JAKs) represent a class of tyrosine kinases. The JAK signaling pathway is pivotal for the downstream signaling of inflammatory cytokines, including interleukins, interferons, and multiple growth factors. This article provides an overview of [...] Read more.

Named after the two-faced Roman god of doorways, Janus kinases (JAKs) represent a class of tyrosine kinases. The JAK signaling pathway is pivotal for the downstream signaling of inflammatory cytokines, including interleukins, interferons, and multiple growth factors. This article provides an overview of the JAK pathway and signaling, its significance in immune-mediated dermatologic diseases and the development of a targeted, localized option of a selective JAK inhibitor, ruxolitinib cream. In the early 1990s, various discovery and clinical development programs were initiated to explore pharmaceutical inhibition of the JAK-STAT pathway. Incyte Corporation launched a strategy to identify molecules suitable for both topical as well as oral delivery. Ruxolitinib was designed as a molecule with low nanomolar potency selective for JAK1 and 2 enzymes, but without significant inhibition of non-JAK kinases, as well as physicochemical properties for both topical and oral administration. An oil-in-water emulsified ruxolitinib cream formulation was developed for topical application and was studied in multiple immune-mediated dermatologic diseases including psoriasis, alopecia areata, atopic dermatitis and vitiligo. Ruxolitinib cream represents a novel, JAK1/2 selective therapy that can be delivered directly to the skin to treat a number of cytokine-driven, inflammatory dermatoses. Full article

(This article belongs to the Special Issue Skin Immunomodulation: Impact on Diseases and Treatments)

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