The present study was focused on the development of surface modified gelatin nanoparticles (SGNPs) using novel ligand 4-sulfated N-acetyl galactosamine (4-SO4GalNAc) for specific targeting to macrophages. The gelatin has been modified with the potential targeting moiety 4-SO4GalNAc, which was further used for the preparation of modified nanoparticles. The nanoparticles have been prepared by two step desolvation method. The SGNPs and unmodified gelatin nanoparticles (GNPs) were loaded with doxorubicin (DxR) and its targeting potential was compared. Developed DxR loaded SGNPs (DxR-SGNPs) were found to have negative zeta potential (-19.8±0.22 mV) whereas DxR loaded GNPs (DxR-GNPs) have the positive zeta potential of around +12.2±0.36 mV. The mean particle size of DxR-SGNPs and DxR-GNPs was found to be 283±7nm and 134±5 nm respectively. Flow cytometric data confirmed the enhanced uptake of DxR-SGNPs in J774A.1 and PBMC when compared with DxR-GNPs. Intracellular localization studies indicate that the fluorescence intensity of DxR-SGNPs was significantly higher when compared to DxR-GNPs. DxR-SGNPs rendered significantly higher localization of DxR in liver and spleen as compared to DxR-GNPs after i.v. administration. The study stipulates that 4-SO4GalNAc assures for targeting resident macrophages
