A cell-mimicking platelet-based drug delivery system as a potential carrier of dimethyl fumarate for multiple sclerosis

Abstract

Dimethyl fumarate (DMF), is one of the lately approved therapeutic agents for the multiple sclerosis (MS) treatment. Despite the beneficial effects, DMF also suffers from low penetration into brain.In this study, we designed a precise drug delivery system of DMF to cross BBB for MS management. The novelty of this study is developing a cell based biomimetic vehicle for specific drug delivery to the inflamed area in peripheral and CNS. DMF-loaded platelet-based nanoparticle as a cell-based drug delivery system was developed and compared with chitosan nanogel and platelet membrane coated chitosan nanogel. Prepared nanoparticles were characterized for particle size, morphology, release characteristics, and drug loading parameters. In the optimum condition, all nanoparticles were prepared in desirable nano-size and showed appropriate loading parameters. The neuropharmacokinetic evaluation was performed by determining the brain uptake of DMF, and brain uptake clearance for passage from BBB. Results from in vivo study demonstrated that the brain concentration of nanoparticles was higher than the free drug solution. The brain uptake clearance and AUC (0-∞) brain of DMF-loaded platelet nanoparticle were higher than platelet membrane coated chitosan nanogel and chitosan nanogel. The results demonstrated that platelet nanoparticles can be proposed as a potential biomimetic carrier for MS management.