Dextran sulfate-modified pH-sensitive layered double hydroxide nanocomposites for treatment of rheumatoid arthritis

To reduce the side effects of methotrexate and increase its anti-inflammatory effect, we developed a drug delivery system, dextran sulfate-modified methotrexate-loaded layered double hydroxide nanocomposites (LDH-MTX-DS), with both targeting and pH-sensitivity for the treatment of rheumatoid arthritis. The nanocomposites had a mean particle size of 303.1 +/- 8.07 nm, zeta potential of - 12.4 +/- 0.7 mV, encapsulation efficiency of 49.64%, and loading efficiency of 16.81%. In vitro release experiments demonstrated that the drug was released faster in PBS at pH 5.5 than at pH 7.4, which reflected the pH-sensitivity of this system. Cellular uptake assays displayed higher cellular uptake rate of the dextran sulfate-modified targeting carrier compared with that of a non-targeting carrier (P < 0.01), which indicated that the LDH-MTX-DS could actively target scavenger receptors on the surface of activated RAW 264.7 cells. In vivo pharmacodynamic experiments showed that, after the second (P < 0.001) and third (P < 0.05) administrations, the preparation group exhibited significantly improved therapeutic efficacy in adjuvant-induced arthritis (AIA) rats when compared with free MTX alone. These results indicated that this drug delivery system was promising in the treatment of rheumatoid arthritis.

Automated summary

A drug delivery system, LDH-MTX-DS, with targeting and pH-sensitivity was developed to reduce the side effects of methotrexate and enhance its anti-inflammatory effect in the treatment of rheumatoid arthritis. The in vitro release experiments showed faster drug release at pH 5.5, while in vivo pharmacodynamic experiments demonstrated significantly improved therapeutic efficacy in adjuvant-induced arthritis rats.