Folate receptor-β targeted cholesterol-chitosan nanocarrier for treatment of rheumatoid arthritis: An animal study

Targeted delivery of drug to the site of inflammation may be useful in better management of the rheumatoid arthritis. Macrophages are available in elevated numbers in the inflamed synovial joint during rheumatoid arthritis and their response to therapy leads to success in anti-rheumatic treatment. To target the macrophages in the inflammatory synovium, we fabricated a methotrexate (MTX) encapsulated, cholesterol grafted chitosan nanocarrier tagged with anti-folate receptor-β antibody (Ab-CCM-NP). Folate receptor-β among other subtypes, alpha and gamma, is highly expressed in inflammatory cells. The nanoparticles exhibited a size of 181 ± 30 nm with a loading efficiency of 63.7 ± 11.1%. The nanoparticle demonstrated extended release capability and a 2.5 fold increase in half life in comparison to the free MTX following intravenous (i.v.) administration with better localization at the inflamed joints achieved due to active targeting. When compared with MTX, i.v. administration of Ab-CCM-NP was successful in significant reduction of paw volume and serum cytokine expression (IL-6 and TNF-α). Histological examination of the joints showed significant reduction of inflammation and edema by Ab-CCM-NP. Our study demonstrates efficacy in active targeting of inflamed joints as a useful modality in rheumatoid arthritis management.