Non-invasive management of rheumatoid arthritis using hollow microneedles as a tool for transdermal delivery of teriflunomide loaded solid lipid nanoparticles

Conventional RA treatments required prolonged therapy courses that have been accompanied with numerous side effects impairing the patient's quality of life. Therefore, microneedles combined with nanotechnology emerged as a promising alternative non-invasive, effective and self-administrating treatment option. Hence, the main aim of this study is to reduce the side effects associated with systemic teriflunomide administration through its encapsulation in solid lipid nanoparticles (TER-SLNs) and their administration through transdermal route using AdminPenTM hollow microneedles array in the affected joint area directly. In vitro characterization studies were conducted including particle size, zeta potential, encapsulation efficiency and in vitro drug release. Also, ex vivo insertion properties of AdminPenTM hollow microneedles array was carried out. Besides, in vivo evaluation in rats with antigen induced arthritis model were also conducted by assessment of joint diameter, histopathological examination of the dissected joints and testing the levels of TNF-& alpha;, IL1B, IL7, MDA, MMP 3, and NRF2 at the end of the experiment. The selected TER-SLNs formulation was about 155.3 nm with negative surface charge and 96.45 % entrapment efficiency. TER-SLNs had a spherical shape and provided sustained release for nearly 96 h. In vivo results demonstrated that nanoencapsulation along with the use of hollow microneedles had a significant influence in improving TER anti-arthritic effects compared with TER suspension with no significant difference from the negative control group.