title: Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model.
abstract: Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na) were blended with PAA(-) Na(+) and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of -0.7 (+/-0.2), and incorporated approximately 20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 microg g(-1) or single dosage of 15 microg g(-1) in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 microg g(-1) revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.
authors.affiliation: Department of Large Animal Clinical Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Ranjan
authors.forename: Nikorn
authors.initials: N
authors.lastname: Pothayee
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Seleem
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Tyler
authors.forename: Bonnie
authors.initials: B
authors.lastname: Brenseke
authors.forename: Nammalwar
authors.initials: N
authors.lastname: Sriranganathan
authors.forename: Judy S
authors.initials: JS
authors.lastname: Riffle
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Kasimanickam
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D005839:Gentamicins / Q000008:administration & dosage* / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D050997:Nanomedicine / Q000379:methods; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012475:Salmonella / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D012480:Salmonella Infections / Q000188:drug therapy* / Q000382:microbiology*; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D005839:Gentamicins