Targeted delivery of methotrexate by modified yeast β-glucan nanoparticles for rheumatoid arthritis therapy.

The linear β-(1, 3)-glucans from yeast (BYGs) with good biocompatibility and targetability to macrophages were used for fabricating BYG-based nanoparticles to deliver methotrexate with systemic toxicity for treatment of rheumatoid arthritis. Methoxy poly (ethylene glycol) (mPEG) was successfully grafted onto BYGs chains, followed by chemical crosslinking to get the crosslinked copolymer (cBP) with amphiphilicity, which could self-assemble into spherical nanoparticles (ca.52.9 nm in diameter). The methotrexate-loaded cBP nanoparticles (cBPM) with the drug loading efficiency of 23.7% was proved to linearly release methotrexate due to reduction of disulfide bonds by glutathione. Cell experiments demonstrate that cBP nanoparticles were effectively internalized into macrophages due to the targetability. Animal experiments show that cBPM were highly targeted to the inflamed tissue, leading to macrophage transformation from M1 to M2 type and reduction of pro-inflammatory factors. This work provides an alternative safe strategy for the clinical treatment of rheumatoid arthritis with β-glucan nanoparticles as carrier.