Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.

Highly Biocompatible Smart Injectable Hydrogel for the Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that severely affects joints and restricts locomotion. Various treatment regimens are available for RA, providing short-term relief from pain, but long-term relief from the disease is still not available. Evidently, cytokines play a crucial role in the pathophysiology of the disease. However, aberrant immune responses, genetic dispositions, viral infections, or toxicants are some possible causative mediators of RA. The synovial fluid of rheumatoid arthritis patients encompass cytokines, especially osteoclastogenic cytokines, and invasion factors such as macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). Moreover, tumor necrosis factor-α (TNF-α) and interleukins (IL-1, 6, and 17) intensify osteoclast differentiation and activation. Therefore, in order to restrict the cytokine expression, we used budesonide as a therapeutic lead and encapsulated it into a highly biocompatible hydrogel system. The hydrogel system developed by us is enzyme-responsive and provides sustained drug release flow over an extended period of time. This hydrogel is characterized by ζ-potential analysis, field-emission scanning electron microscopy (FE-SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and it is further encapsulated with budesonide (glucocorticoids) for therapeutic purposes. Evidently, Bud-loaded ER-hydrogel showed improvement in joint physiology compared to the disease group and downregulated the inflammatory markers.