ABSTRACT

Nanostructured lipid carriers (NLCs) are considered as novel drug delivery vehicles because of their higher loading capacity, better surface area, enhanced drug solubility and improved bioavailability of hydrophobic compounds, and also in controlling the drug release in a better manner than conventional solid lipid nanoparticles (SLNs). A “biphasic release pattern”, i.e., the initial fast release and subsequent sustained release of the methotrexate (MTX), an anti-inflammatory drug used in the treatment of rheumatoid arthritis, from NLCs has been observed in vitro. NLCs showed greater uptake and overexpression of inflammatory mediators, along with apoptosis in HaCat and U937 cells. The immunocytochemistry and immunofluorescence studies advocated reduced inflammation and triggered apoptosis via the overexpression of proapoptotic gene, Bim, which in turn was regulated by NF-κB and FOXO1 pathways, stimulated by NLCs-loaded MTX in an experimental in vitro model of rheumatoid arthritis. The formulated NLCs showed better skin permeation and safety potential. In conclusion, these features accomplished NLCs as an attractive tool for targeted drug delivery in rheumatoid arthritis and other similar inflammatory disorders.