Rheumatoid arthritis is a chronic autoimmune disease, with the features of recurrent chronic inflammation of synovial tissue, destruction of cartilage, and bone erosion, which further affects joints tissue, organs, and systems, and eventually leads to irreversible joint deformities and body dysfunction. Therapeutic drugs for rheumatoid arthritis mainly reduce inflammation through regulating inflammatory factors. Transdermal administration is gradually being applied to the treatment of rheumatoid arthritis, which can allow the drug to overcome the skin stratum corneum barrier, reduce gastrointestinal side effects, and avoid the first-pass effect, thus improving bioavailability and relieving inflammation. This paper reviewed the latest research progress of transdermal drug delivery in the treatment of rheumatoid arthritis, and discussed in detail the dosage forms such as gel (microemulsion gel, nanoemulsion gel, nanomicelle gel, sanaplastic nano-vesiclegel, ethosomal gel, transfersomal gel, nanoparticles gel), patch, drug microneedles, nanostructured lipid carrier, transfersomes, lyotropic liquid crystal, and drug loaded electrospinning nanofibers, which provide inspiration for the rich dosage forms of transdermal drug delivery systems for rheumatoid arthritis.

In recent years, cancer immunotherapy has emerged as an exciting cancer treatment. Immune checkpoint blockade brings new opportunities for more researchers and clinicians. Programmed cell death receptor-1 (PD-1) is a widely studied immune checkpoint, and PD-1 blockade therapy has shown promising results in a variety of tumors, including melanoma, non-small cell lung cancer and renal cell carcinoma, which greatly improves patient overall survival and becomes a promising tool for the eradication of metastatic or inoperable tumors. However, low responsiveness and immune-related adverse effects currently limit its clinical application. Overcoming these difficulties is a major challenge to improve PD-1 blockade therapies. Nanomaterials have unique properties that enable targeted drug delivery, combination therapy through multidrug co-delivery strategies, and controlled drug release through sensitive bonds construction. In recent years, combining nanomaterials with PD-1 blockade therapy to construct novel single-drug-based or combination therapy-based nano-delivery systems has become an effective mean to address the limitations of PD-1 blockade therapy. In this study, the application of nanomaterial carriers in individual delivery of PD-1 inhibitors, combined delivery of PD-1 inhibitors and other immunomodulators, chemotherapeutic drugs, photothermal reagents were reviewed, which provides effective references for designing new PD-1 blockade therapeutic strategies. Graphical Abstract

Based on the opportunities of ibuprofen administration innovation and challenges associated with the construction of transdermal drug delivery systems using medicated nanoparticles and electrospun nanofiber membranes, we developed a transdermal drug delivery system comprising ibuprofen-loaded ZnO nanoparticles/polyacrylonitrile electrospun nanofiber membranes (ZnO-ibuprofen/PAN), which was dual-stimulus responsive, wherein both pH and temperature triggered drug release. ZnO-ibuprofen nanoparticles with high drug loading capacity (17.7%) were prepared at room temperature by a one-step method involving 4,4′-((4-(4H-1,2,4-triazol-4-yl) phenyl) azanediyl)dibenzoic acid, Zn(NO3)2·6H2O, and ibuprofen, following which electrospinning was conducted to generate the ZnO-ibuprofen/PAN nanofibers. The transdermal drug release behavior of the ZnO-ibuprofen/PAN electrospun nanofiber membranes in the normal (pH = 7.4, 37 °C) and inflammatory (pH = 6.5, 42 °C) tissue environment exhibited increased drug release rate at higher ambient temperatures and decreased pH following 24 h of drug release. The cumulative drug release rate of ZnO-ibuprofen/PAN electrospun fibers through porcine skin under inflammatory conditions reached 71.35% ± 2.96% after 24 h, thereby demonstrating their favorable transdermal permeation behavior. The cytotoxicity assays revealed that the nanofibers possessed excellent biocompatibility. Thus, the dual stimulus-responsive ZnO-ibuprofen/PAN can be an effective transdermal drug delivery carrier.