RESUMEN
Macroporous three-dimensional (3D) framework structured melamine foam-based Enzyme-Linked Immunosorbent Assay (f-ELISA) biosensors were developed for rapid, reliable, sensitive, and on-site detection of trace amount of biomolecules and chemicals. Various ligands can be chemically immobilized onto the melamine foam, which brings in the possibility of working with antibodies, nanobodies, and peptides, respectively, as affinity probes for f-ELISA biosensors with improved stability. Different chemical reagents can be used to modify the foam materials, resulting in varied reactivities with antibodies, nanobodies, and peptides. As a result, the f-ELISA sensors produced from these modified foams exhibit varying levels of sensitivity and performance. This study demonstrated that the chemical reagents used for immobilizing antibodies, nanobodies, and peptides could affect the sensitivities of the f-ELISA sensors, and their storage stabilities under different temperatures varied depending on the sensing probes used, with f-ELISA sensors employing nanobodies as probes exhibiting the highest stability. This study not only showcases the versatility of the f-ELISA system but also opens new avenues for developing cost-effective, portable, and user-friendly diagnostic tools with optimized sensitivity and stability.
RESUMEN
Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p < 0.0001), PSI (p < 0.0001) and epidermal thickness (p < 0.05). Moreover, a strengthened anti-inflammatory effect caused by TYK2i-BO-gel is seen in a human skin explant model, implying its potential application for human patients. With the addition of BO, the TYK2i-BO-gel not only increases skin permeability but also inhibits the expression of antimicrobial peptides in keratinocytes and facilitates the anti-Th17 response of TYK2i with suppressed activation of STAT3. Therefore, this work represents the accessibility and effectiveness of TYK2i-BO-hydrogel as a new topical formulation for anti-psoriasis management and shows great potential for clinical application.