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Abstract
Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than −16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 μg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of uncertain cause that affects1% of the population of the developed world, being more common among women than men, with 80%of the total cases occurring between the ages of 35 and 50 [1]
The properties and characteristics of the NPs influence the formulation stability and can influence their future interactions with cells and tissues [22,23], so they were characterized in terms of NP size, polydispersion index (PdI), Zeta potential as well as MTX content and superparamagnetic iron oxide nanoparticles (SPIONs) co-localization
The use of solid lipid nanoparticles (SLN) for simultaneous in vivo imaging and drug delivery is an interesting approach for safe theranostic applications considering their biocompatibility and biodegradability, especially with the new possibilities of multifunctionalization brought by nanomedicine
Summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of uncertain cause that affects1% of the population of the developed world, being more common among women than men, with 80%of the total cases occurring between the ages of 35 and 50 [1]. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of uncertain cause that affects. RA is often induced by an external agent (like cigarette smoking, infection or trauma) that triggers an autoimmune reaction, leading to synovial hypertrophy and chronic joint inflammation along with potential for extra-articular manifestations [1,2]. Superparamagnetic iron oxide nanoparticles (SPIONs) have been proven to be very effective and versatile as MRI contrast agents for a variety of different applications [6]. Methotrexate (MTX) is one of the dominant drugs used in RA management, a low-cost disease-modifying anti-rheumatic drug that seems to exert its anti-inflammatory effects by acting at different levels of the pathophysiological signaling cascade [2,7]. MTX has proven to be effective against RA; the non-specific administration of MTX leads to accumulation and subsequent damage of healthy tissues [1,2,4]
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