Development and characterization of sulfasalazine loaded fucosylated PPI dendrimer for the treatment of cytokine-induced liver damage

作者：Gupta Richa; Mehra Neelesh Kumar; Jain Narendra Kumar^*

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2014, 86(3): 449-458.

DOI：10.1016/j.ejpb.2013.10.018

• Fucose
• PPI dendrimers
• Kupffer cells
• Sulfasalazine
• Targeting
• Macrophages
• Pharmacokinetic

The present investigation was aimed at exploring the targeting potential of sulfasalazine (NF-kappa B inhibitor drug) loaded fucose tethered poly (propylene imine) (PPI) dendritic nanoarchitecture (SSZ-FUCO-PPID) to Kupffer cells for effective management of cytokine-induced liver damage. The SSZ-FUCO-PPID formulation was characterized for entrapment efficiency, in vitro release, stability, toxicological investigations, macrophage uptake, NF-kappa B inhibition, and in vivo studies. In cell uptake assay the uptake of SSZ-FUCO-PPID was found to be higher and preferentially by J774 macrophage cell line. Cytokine assay suggested that the SSZ-FUCO-PPID potentially inhibited the IL-12 p40 production in LPS activated macrophages. Western blot analysis clearly suggested that SSZ-FUCO-PPID inhibited the activation of NF-kappa B as indicated by the absence of p-I kappa B band. Pharmacokinetic study revealed improved bioavailability, half-life and mean residence time of SSZ upon fucosylation of dendrimers. The biodistribution pattern clearly established the higher amount of SSZ-FUCO-PPID in liver. Hematological data suggest that the fucosylated formulations are less immunogenic as compared to unconjugated formulations. The results suggest that the SSZ-FUCO-PPID formulation holds targeting potential to Kupffer cells for the treatment of cytokine-induced liver damage.

• 出版日期2014-4