Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model


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.

Life Sciences & Biomedicine, Nanoscience & Nanotechnology, Pharmacology & Pharmacy, Science & Technology - Other Topics, gentamicin, core-shell nanostructures, Salmonella, PLURONIC(R) BLOCK-COPOLYMERS, INDUCED NEPHROTOXICITY, DRUG-DELIVERY, LIPOSOMES, NANOPARTICLES, NANOCARRIERS, RELEASE, 0601 Biochemistry and Cell Biology, 1007 Nanotechnology, 1115 Pharmacology and Pharmaceutical Sciences, Nanoscience & Nanotechnology