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Antimicrobial Agents and Chemotherapy, April 2007, p. 1310-1314, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00890-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Loaded onto Albumin Nanoparticles: In Vitro and In Vivo Activities against Brucella abortus{triangledown}

S. Segura,1 C. Gamazo,2 J. M. Irache,1 and S. Espuelas1*

Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, 31008 Pamplona, Spain,1 Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Navarra, 31008 Pamplona, Spain2

Received 19 July 2006/ Returned for modification 30 October 2006/ Accepted 5 January 2007

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.

* Corresponding author. Mailing address: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, 31008 Pamplona, Spain. Phone: 34948425600. Fax: 34948425649. E-mail: sespuelas{at}unav.es

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1310-1314, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00890-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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