Produção, caracterização e avaliação biológica de nanopartículas carregadas com metotrexato e hidroxicloroquina para o tratamento da Artrite Reumatoide

Abstract

Rheumatoid arthritis (RA) is a chronic immune-mediated multisystemic disease that is mainly located in the joints. It is the most common systemic inflammatory rheumatic disease, affecting approximately 1% of the world's population. Although a precise etiology has yet to be determined, RA is a multifactorial disease, with a complex interaction between the host and the environment determining the overall risk of disease susceptibility, persistence and severity Disease progression is associated with inability to perform activities costs, systemic complications, early death and socioeconomic costs. RA is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction, and systemic manifestations such as pulmonary, cardiovascular, and neurological involvement. Current therapeutic approaches for the treatment of RA aim at reducing joint damage and at early and persistent remission of the disease. However, despite advances in diagnosis and gradual adoption of new drugs, there is still a substantial gap in disease management, with many patients failing to achieve considerable and sustained clinical responses, demonstrating modest long-term results. Currently, conventional disease-modifying anti-rheumatic drugs (DMARDs) are the recommended first-line therapy, in particular methotrexate (MTX) and (HCQ). Despite their therapeutic potential, low cost and well-established safety and toxicity profile, DMARDs induce considerable side effects that vary according to the patient, time of treatment and administered dose. In this study, we developed a new drug delivery system with Pluronic® F-127 nanoparticles co-loaded with HCQ and MTX and the effects evaluated in a model of antigenic induced arthritis in mice. The results obtained show that nanoparticles loaded with drugs were able to modulate the inflammatory process of RA and reduce osteoclastogenesis, edema and cell migration to the joint. Overall, drug-loaded nanoparticles showed a 2-fold greater therapeutic effect compared to free drugs. These findings suggest the possibility of developing a drug delivery nanosystem capable of achieving therapeutic efficiencies observed in clinical practice, but with a reduction in the administered dose