Revolutionizing rheumatoid arthritis treatment with emerging cutaneous drug delivery systems: overcoming the challenges and paving the way forward.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the articulating joints. Though considerable progress has been made in understanding the disease in the past 50 years, its pathogenesis remains unclear. The therapies for RA, such as nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and glucocorticoids through conventional therapeutic delivery systems by percutaneous, intra-articular, intraperitoneal, oral, and intravenous administration, have shown their own disadvantages, which eventually reduce patient compliance for long-term therapy. Recently, drug delivery via a topical or transdermal route has gained attention as an alternative to the conventional approach. Though skin acts as a barrier for the delivery of drugs due to its structure, various permeation pathways are manipulated to enhance the drug delivery across or into the skin. However, poor skin retention is the reason for the failure of many conventional topical dosage forms, such as gels, sprays, and creams. Hence, there is an urgent need for conquering the skin boundary to improve skin partitioning. Nanotechnology is a developing and dynamic field gaining popularity in the nanoscale design. This review extensively describes the potential of various nanoformulations, such as vesicular systems, lipid nanoparticles, and polymeric nanoparticles, with a targeted approach to deliver the drugs to the inflamed joint region. Limelight has also been provided to next-generation approaches like surface modification, stimuli-responsive formulations, multifunctional carrier systems, microneedles, and microsponge systems. Physical methods for enhancing the transdermal delivery, such as electroporation and sonophoresis, and emerging treatment therapies, such as gene therapy, photothermal therapy, and photodynamic therapy, have been evaluated to enhance the treatment efficacy. The clinical status, patents and current challenges associated with nanotechnology and the future prospects of targeted drug delivery have also been discussed.