Gamma interferon loaded onto albumin nanoparticles: in vitro and in vivo activities against Brucella abortus.
The aim of this study was to evaluate the activity of gamma interferon (IFN-gamma) when it was either adsorbed onto or loaded into albumin nanoparticles. Brucella abortus-infected macrophages and infected BALB/c mice were selected as the models for testing of the therapeutic potentials of these cytokine delivery systems, in view of the well-established role of IFN-gamma-activated macrophages for the control of Brucella sp. infections. Whereas the encapsulation of IFN-gamma inside the matrix of nanoparticles completely abrogated its activity, adsorbed IFN-gamma increased by 0.75 log unit the bactericidal effect induced by RAW macrophages activated with free IFN-gamma, along with a higher level of production of nitric oxide. In infected BALB/c-mice, IFN-gamma adsorbed onto nanoparticles was also more active than free cytokine in reducing the number of bacteria in the spleens, and the effect was mediated by an increased ratio of IFN-gamma-secreting (Th1) to interleukin-4-secreting (Th2) cells. Overall, albumin nanoparticles would be suitable as carriers that target IFN-gamma to macrophages and, thus, potentiate their therapeutic activity.
Segura
S
S
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, 31008 Pamplona, Spain.
Gamazo
C
C
Irache
J M
JM
Espuelas
S
S
D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D002003:Brucella abortus / Q000187:drug effects*; D002006:Brucellosis / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*
D000418:Albumins; D004337:Drug Carriers; D007371:Interferon-gamma