L-Arginine-Modified Chitosan Curcumin Nanocrystals Target M1 Macrophages via CAT-2/Clathrin-Mediated Endocytosis for Mitochondrial Protection and ALI/ARDS Therapy

Background: Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a fatal inflammatory disorder driven by M1 macrophages and the associated inflammatory cascade. Targeted drug delivery to these cells is a promising therapeutic strategy. Methods: L-arginine was conjugated to chitosan of different molecular weights. The resulting curcumin nanocrystals (Arg-CS-Cur) were characterized for conjugation efficiency, zeta potential, stability, and drug release profile. Cellular uptake mecha