PMC

Electrophoresis. Red boxes: free proteins; blue boxes: dimerized proteins; yellow boxes: proteins grafted onto SLNs. (A) ST-MBS; 8:1 2-iminothiolane/TRF molar ratio; (B) ST-MBS; 4:1 2-iminothiolane/TRF molar ratio; (C) ST-MBS; 2:1 2-iminothiolane/TRF molar ratio; (D) ST-MBS; 1:1 2-iminothiolane/INS molar ratio; (E) ST-PEG-MBS; 2:1 2-iminothiolane/TRF molar ratio; (F) ST-PEG-MBS; 1:1 2-iminothiolane/INS molar ratio.

Biodistribution of the unfunctionalized ddMTX-loaded SLNs and free MTX (sacrifice 30 min after administration). Statistical analysis: ddMTX-loaded SLNs vs. free MTX; stearic acid SLNs < MTX: p < 0.005 **; behenic acid SLNs < MTX: p < 0.05 @; behenic acid SLNs > MTX: p < 0.05 #, p < 0.001 ###; behenic acid SLNs PVA120000 > MTX: p < 0.1 §, p < 0.01 §§, p < 0.05 §§§.

Permeation through the hCMEC/D3 cells monolayer of unfunctionalized and functionalized ddMTX-loaded behenic acid SLNs and free MTX. Statistical analysis: ddMTX-loaded SLNs vs. free MTX; SLNs TRF ST-PEG-MBS<MTX: p < 0.05 *; SLNs INS ST-PEG-MBS<MTX: p < 0.1 $; SLNs > MTX: p < 0.1 #, p < 0.05 ##; SLNs TRF ST-PEG-MBS>MTX: p < 0.1 §, p < 0.05 §§; SLNs INS ST-PEG-MBS > MTX: 24 h p < 0.005 °; SLNs TRF ST-MBS>MTX: p < 0.05 ç; SLNs INS ST-MBS > MTX: p < 0.05 @, p < 0.005 @@.

Biodistribution of functionalized ddMTX-loaded SLNs and free MTX (sacrifice 3 h after administration): in (A) the whole body and (B) brain and capillary depletion (cap. dep.). Statistical analysis: ddMTX-loaded SLNs vs. free MTX; SLNs < MTX: p < 0.01 £ SLNs INS ST-PEG-MBS < MTX: p < 0.05 *; SLNs INS ST-MBS < MTX: p < 0.01 $, p < 0.05 $$; SLNs > MTX: p < 0.1 #, p < 0.05 ##; SLNs TRF ST-PEG-MBS > MTX: p < 0.1 §, p < 0.05 §§, p < 0.01 §§§; SLNs INS ST-PEG-MBS>MTX: p < 0.1 °, p < 0.05 °°; SLNs TRF ST-MBS > MTX: p < 0.1, ST-MBS > MTX: p < 0.1 @.