Integrating 3D-printed hydrogels and polymeric nanofibers in a double-layered transdermal patch for the treatment of rheumatoid arthritis†

Abstract

Patients with rheumatoid arthritis (RA), an inflammatory illness that affects the synovial joints, have a much worse quality of life. Mostly, oral or injectable formulations are used to treat RA, underscoring the critical need for an innovative medication delivery method to enhance therapeutic outcomes and patient compliance. The present study integrated 3D bioprinting and electrospinning technologies to create a unique double-layered transdermal patch (TDDP) for the treatment of RA. The first layer was prepared by 3D-printing a newly developed hydrogel (HG) containing hyaluronic acid (HA) that maintains the joint components and dexamethasone (DEX), an anti-inflammatory agent. A second layer of electrospun polycaprolactone (PCL) nanofibers (NFs) loaded with naringin (NAR), an antimicrobial and anti-inflammatory natural plant extract, was fabricated and integrated with the former layer. The morphology of the NFs was investigated using SEM, and their diameter ranged from 156.28 to 220.66 nm. The physicochemical properties of the suggested TDDP were investigated using FTIR and DSC. The DEX-loaded 3D-printed HG was able to release about 98% of the loaded DEX over a period of 10 days. In vivo experiments definitively confirmed the efficacy of the newly developed TDDPs, showcasing a substantial reduction in the levels of proinflammatory cytokines (IL-6 and TNF-α) through sandwich ELISA measurements in Rattus norvegicus plasma samples. Besides, the stained photomicrographs of the ankle joints of the animals confirmed the alleviation of the RA symptoms via reducing cell infiltration with a preserved joint tissue structure.