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NPJ Vaccines Jun 2023
PubMed: 37349361
DOI: 10.1038/s41541-023-00689-9 -
International Journal of Molecular... Mar 2023Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore,...
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.
Topics: Humans; Hydrodynamics; Skin; Administration, Cutaneous; Skin Absorption; Inflammation; Pharmaceutical Preparations
PubMed: 37047256
DOI: 10.3390/ijms24076284 -
In Vivo (Athens, Greece) 2023This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIM
This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup.
PATIENTS AND METHODS
Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol.
RESULTS
The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049).
CONCLUSION
The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.
Topics: Humans; Pilot Projects; Anthralin; Oxidative Stress; Balneology; Psoriasis; Water
PubMed: 36881082
DOI: 10.21873/invivo.13153 -
Prague Medical Report 2023Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair... (Review)
Review
Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair loss, which can have huge psychosocial impact for those affected. Treatment modalities which have been used so far included nonspecific immunosuppressive medications, such as corticosteroids, cyclosporine, and methotrexate, or topical immunomodulators, such as diphencyprone, dithranol, and squaric acid dibutylester. The recognition of the importance of Janus kinase pathway in alopecia areata pathogenesis enabled more specific approaches in treatment. Positive outcomes of Janus kinase inhibitors in several trials granted approval for baricitinib which became the first on-label treatment for alopecia areata. The aim of this review is to summarize the role, efficacy and safety of several Janus kinase inhibitors in alopecia areata.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Janus Kinases; Adjuvants, Immunologic
PubMed: 36763827
DOI: 10.14712/23362936.2023.1 -
International Journal of Biological... Mar 2023Irritant contact dermatitis (ICD) is an inflammatory skin condition characterized by severe eczematous lesions. Nanoparticulate drug delivery is the most predominant way...
Skin targeting by chitosan/hyaluronate hybrid nanoparticles for the management of irritant contact dermatitis: In vivo therapeutic efficiency in mouse-ear dermatitis model.
Irritant contact dermatitis (ICD) is an inflammatory skin condition characterized by severe eczematous lesions. Nanoparticulate drug delivery is the most predominant way to improve dermal penetration and have gained remarkable recognition for targeted delivery of therapeutic payload and reduced off-target effects. Therefore, the current work aimed to fabricate polyelectrolyte complex nanoparticles (PENPs) containing two natural biodegradable polymers namely; chitosan (CS) and hyaluronic acid (HA) to deliver the non steroidal anti-inflammatory drug etoricoxib (ETX) to the deeper skin layers to alleviate any systemic toxicity and improve its therapeutic efficacy against ICD. ETX loaded-PENPs were prepared and optimized utilizing three independent variables; CS: HA mass ratio, chitosan solution pH and molecular weight of chitosan. Following the various physicochemical optimizations, the optimum ETX-loaded PENPs formulation (N1 0.15 %) exhibited spherical nature with an average diameter of 267.9 ± 9.4 nm, Polydispersity index of 0.366 ± 0.02, and positive zeta potential (+32.9 ± 0.47 mV). The drug was successfully entrapped and the entrapment efficiency reached 95 ± 0.2 %. N1 0.15 % formula showed efficient dermal targeting by significantly enhanced percentage of ETX permeated and retained in the various skin layers in comparison to ETX conventional gel during the ex-vivo skin permeation experiments. Furthermore, N1 0.15 % exhibited superior anti-inflammatory properties in vivo compared to ETX conventional gel in dithranol induced mice ear dermatitis. Conclusively, ETX-loaded PENPs could be a promising therapeutic approach for effecient management of ICD.
Topics: Mice; Animals; Irritants; Chitosan; Anti-Inflammatory Agents; Hyaluronic Acid; Dermatitis, Contact; Nanoparticles; Dermatitis; Particle Size; Drug Carriers
PubMed: 36709804
DOI: 10.1016/j.ijbiomac.2023.123458 -
Molecules (Basel, Switzerland) Jan 20231,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in...
1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.
Topics: Anthralin; Protons; Electrons; Anthracenes; Alcohols; Ketones
PubMed: 36615539
DOI: 10.3390/molecules28010344 -
Cutis Aug 2022Topical medications have high utility in the treatment of psoriasis because of their localized effect and ability to be used as both monotherapy and adjunctive therapy.... (Review)
Review
Topical medications have high utility in the treatment of psoriasis because of their localized effect and ability to be used as both monotherapy and adjunctive therapy. The American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) published guidelines in 2020 regarding the management of psoriasis with topical therapies. These guidelines are a framework that assist clinicians treating psoriasis patients with topical agents including steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar). This review presents these evidence-based recommendations in a form that dermatologists can readily apply to their clinical practice. The selection of an appropriate topical therapy, effective combination therapies, duration of use, and adverse events are addressed.
Topics: Administration, Topical; Anthralin; Calcineurin Inhibitors; Coal Tar; Dermatologic Agents; Emollients; Humans; Psoriasis; Retinoids; Salicylic Acid; Steroids; Vitamin D
PubMed: 36219602
DOI: 10.12788/cutis.0573 -
NPJ Vaccines Sep 2022Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our...
Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8 T cells and CD4 T cells with a T cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.
PubMed: 36153349
DOI: 10.1038/s41541-022-00530-9 -
International Journal of Dermatology Jan 2023
Topics: Humans; Anthralin; Skin; Psoriasis; Staining and Labeling; Face
PubMed: 36073242
DOI: 10.1111/ijd.16405