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

► A multi-objective optimization approach was used for nanogels preparation. ► The surfaces of the nanogels were modified by polysorbate-80 for brain targeting. ► Acceptable size, poly dispersity index, and drug loading parameters were achieved. ► The surface modified nanogels showed an acceptable release performance in vitro. ► Optimized surface modified nanogels can be a good candidate for brain drug delivery.