Preparation and optimization of surface-treated methotrexate-loaded nanogels intended for brain delivery.

Nanogels loaded with methotrexate (MTX) were prepared via an ionic gelation process using chitosan and sodium tripolyphosphate (TPP). The preparation process was optimized by a systematic multi-objective-optimization approach in terms of the size, poly-dispersity index (PDI), loading efficiency (LE) and loading capacity (LC) of the resulting nanocarriers. A combination of the pH of the chitosan solution, the addition time of the TPP solution and temperature effects accounted for nearly 75% of the variation in nanogel size; the TPP initial concentration had a very significant effect on LE (p<0.0001). The final particle size (Z-average (r nm)), PDI, LE and LC corresponding to the optimal conditions were 59.27 nm, 0.34, 61.82% and 53.68%, respectively. As the ultimate goal, the surfaces of the MTX-loaded nanogels were modified by polysorbate 80 for the purpose of brain targeting. The cumulative in vitro release profiles of surfactant-coated and uncoated nanogels were almost identical and showed acceptable performance.