Tofacitinib in focus: Fascinating voyage from conventional formulations to novel delivery systems.

Tofacitinib, a Janus kinase (JAK) inhibitor, has emerged as a primary therapeutic agent for managing autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, dermatitis and ulcerative colitis. By inhibiting the phosphorylation of JAK enzymes, tofacitinib prevents their activation within the JAK-STAT signaling pathway, which is vital for inflammatory responses. However, the tofacitinib delivery presents significant challenges, including pH-dependent solubility, poor permeability and susceptibility to oral degradation. This review provides an in-depth analysis of current and emerging formulations to enhance the delivery and efficiency of tofacitinib. This review highlights the physicochemical, pharmacodynamic and pharmacokinetic properties of tofacitinib. Additionally, it discusses various strategies, including oral modified release formulations, topical/transdermal delivery utilizing lipid-based and polymeric systems, and parenteral delivery systems. Recent advancements in nanotechnology, such as liposomes, micelles, keratinocyte exosomes, proposomes, proglycosomes, transethosomes, squalenyl nanoparticles and lyotropic liquid crystalline nanoparticles, are explored as potential nanocarriers to existing delivery constraints. The development of advanced tofacitinib delivery systems can address the challenges in its delivery and improve therapeutic outcomes and patient compliance, paving the way for enhanced treatment strategies in autoimmune and inflammatory conditions.