title: Development and characterization of sulfasalazine loaded fucosylated PPI dendrimer for the treatment of cytokine-induced liver damage.
abstract: The present investigation was aimed at exploring the targeting potential of sulfasalazine (NF-κB 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-κB 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-κB as indicated by the absence of p-IκB 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.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India. Electronic address: neelesh81mph@gmail.com.
authors.forename: Neelesh Kumar
authors.initials: NK
authors.lastname: Mehra
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India. Electronic address: dr.jnarendr@gmail.com.
authors.forename: Narendra Kumar
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D001388:Aziridines / Q000008:administration & dosage / Q000737:chemistry*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy*; D016207:Cytokines / Q000633:toxicity*; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005643:Fucose / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000008:administration & dosage / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001388:Aziridines; D016207:Cytokines; D050091:Dendrimers; D005643:Fucose; D012460:Sulfasalazine; C031132:propyleneimine
keywords: Fucose; Kupffer cells; Macrophages; PPI dendrimers; Pharmacokinetic; Sulfasalazine; Targeting