Fabrication & characterization of hyaluronic acid/eucalyptus hydrogels loaded with PLGA nanoparticles with methotrexate as an Injectable therapy for rheumatoid arthritis

Abstract

Rheumatoid arthritis is an autoimmune disease that affects about 250,000 Colombians, 82% of whom are women. Current treatments include disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), analgesics and physiotherapy. The most common DMARD is MTX, which binds to plasma proteins with low efficiency (50%) and has a half-life of 6 hours. Due to its limitations when administered orally, nanoparticles (NPs) have been proposed to overcome these limitations. NPs support the release of therapeutic molecules, minimizing side effects and increasing the bioavailability of the drug in a controlled administration. NPs synthesized from biodegradable polymers, such as polyglycolic lactic acid (PLGA), are convenient for drug delivery due to their high biocompatibility and ability to bind DMARDs such as MTX. PLGA NPs loaded with MTX (MTX-PLGA-NPs) have reduced the presence of proinflammatory factors such as IL-10 and TGF-{beta}, suggesting their potential as anti-inflammatory therapies for arthritis. Therefore, this study aims to develop MTX-PLGA-NPs in bioactive and biocompatible hyaluronic acid-eucalyptus (GelHA-E) hydrogels to preserve their stability and delay their degradation. PLGA-NPs were synthesized with an average hydrodynamic diameter of 200 nm, the 1237 cm-1 band found in FITR indicated the successful covalent conjugation with MTX; the mass loss of only 1% in GelHA-E indicated the thermogravimetric stability of the biomaterial and the low hemolytic and platelet aggregation percentage confirmed the biocompatibility of the biomaterial as a potential localized, anti-inflammatory, and injectable treatment for rheumatoid arthritis.