Engineered High-Loaded Mixed-Monoclonal Antibodies (Adalimumab, Rituximab and Trastuzumab) Polymeric Nanoparticle for Rheumatoid Arthritis Treatment: A Proof of Concept

Abstract

Rheumatoid arthritis, a chronic disease, affects from 0.5% to 1% of the world population. The main consequences include loss of joint functionality and severe pain, with lost in life quality and increased risk of morbidity and mortality. The main strategy for RA treatment relies in early diagnosis as targeted therapy. In this regard, the development and application of designed/engineered nanoparticles may represent an innovative approach and the key to success, since is a personalized nanodrug. Thus, we have synthetized, characterized, and in vivo evaluated a tri-loaded monoclonal antibody nanoparticle. For the production we used a mix of monoclonal antibodies: adalimumab, rituximab and trastuzumab to surround all RA metabolic pathways. The characterization included atomic force microscopy, dynamic light scattering analysis and entrapment efficacy using BCA analysis. The in vivo evaluation was done in mice. At this stage we used animals to assess the pharmacokinetics, the tissue distribution as the proof of concept (therapeutic efficacy) of the nanoparticles developed in inducted animals with rheumatoid arthritis. The interpretation of our results revealed that a spherical shaped nanoparticle has been produced with a mean size of 229.7 nm, and a polydispersity index of 0.191. This data has been corroborated by DLS and AFM analysis. The pre-clinical (in vivo) evaluation demonstrated a low elimination rate of 2,34 L/hour, with a purge of 0,42 h. The therapeutic efficacy showed that the nanoparticles have an increased therapeutic effect than the conventional drug with a reduction in all main parameters including the interleukins.