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Methotrexate is successfully used as the gold standard for managing moderate-to-severe psoriasis. However, the low bioavailability and short half-life of the oral pills and the invasiveness of the parenteral injections make these suboptimal therapeutic options. Microneedles, bridging the advantages of the former forms, are successfully used to deliver methotrexate for different therapeutic purposes. However, the utilized dissolving microneedles demand frequent administration, potentially compromising patients' compliance. Additionally, the high toxicity of methotrexate prompts a quest for safer alternatives. Phloretin, a natural compound with confirmed antipsoriatic potential, emerges as a promising candidate. Herein, microneedle patches with separable, slow-degrading tips are developed for the sustained delivery of methotrexate and phloretin, as a comprehensive solution for long-term psoriasis management. Both compounds are individually loaded at varying doses and display sustained-release profiles. The developed microneedle patches demonstrate high mechanical strength, favorable drug delivery efficiency, and remarkable antipsoriatic potential both in vitro in keratinocytes and in vivo in a psoriasis mouse model. Comparative analysis with two subcutaneous injections reveals a similar antipsoriatic efficacy with a single patch of either compound, with prominent phloretin safety. Therefore, the developed patches present a superior alternative to methotrexate's current marketed forms and provide a viable alternative (phloretin) with comparable antipsoriatic efficacy and higher safety., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Tympanokeratomas (cholesteatomas) are destructive keratinic masses of the middle ear that are often treated surgically. In humans, nonechoplanar (non-EP) diffusion-weighted (DW) MRI is efficient in diagnosing tympanokeratomas and differentiating recurrent tympanokeratomas from granulation or fibrous tissue after surgery. The objectives of this study were to (1) determine the characteristics of non-EP DWI of histologically or cytologically confirmed canine tympanokeratomas, (2) determine the performance of non-EP DW images, apparent diffusion coefficient (ADC) map and ADC values in discriminating between tympanokeratomas and other causes of otitis media in dogs, and (3) find an optimal ADC cut-off value. Medical records of dogs diagnosed on MRI with otitis media in two veterinary hospitals were retrospectively reviewed. Sixty-two ears with a cytological or pathological diagnosis of either tympanokeratoma (36/62) or nontympanokeratoma otitis media (26/62) were selected. Diffusion-weighted images had an accuracy of 77.4%, a sensitivity of 94.4%, and a specificity of 53.8% for the detection of tympanokeratoma. The ADC value of middle ear content ranged from 517 to 1355.10 -6  mm 2 /s in tympanokeratoma and from 454 to 2447 × 10 -6  mm 2 /s in nontympanokeratoma otitis media. An ADC value below 916 × 10 -6  mm 2 /s interpreted as a tympanokeratoma yielded an accuracy of 78.7%, a sensitivity of 92.6%, and a specificity of 60%. In the study population, combined qualitative analysis of DW images and ADC maps was the most effective method for diagnosing tympanokeratomas with an accuracy of 80.9%, a sensitivity of 92.6%, and a specificity of 65%., (© 2024 The Author(s). Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment.

Microneedle (MN) technology offers a promising platform for the delivery of a wide variety of active pharmaceutical compounds into and/or through the skin. Yet, the low loading capacity of MNs limits their clinical translation. The solid state of loaded compounds, crystallinity versus amorphousness and crystal size of the former, could greatly affect their loading. Here, we investigated the effect of the crystal size of crystalline compounds on their loading into dissolving MNs, prepared using the solvent-casting technique. A model crystalline compound was subjected to crystal size reduction via wet bead milling and loaded into dissolving MNs. A range of crystal sizes, from micro to nano, was obtained via different milling periods. The obtained crystals were characterized for their size, morphology, and sedimentation behavior. Besides, their content, solid state inside the MNs, and impact on the MN mechanical strength were assessed. The crystals exhibited size-dependent sedimentation, which dramatically affected their loading inside the MNs. However, crystal size and sedimentation demonstrated a negligible effect on the mechanical strength and sharpness of the needles, hence no anticipated impact on the MNs' drug delivery efficiency. The elucidation of the correlation between the crystal size and MN loading opens new potentials to address a major drawback in MN technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)