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Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

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Abstract

Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

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Acknowledgments

This work was supported by the Virginia Tech Institute for Critical Technology and Applied Sciences (ICTAS) and the National Science Foundation under Contract DMR-0805179. We thank Mrs. Kay Carlson and Garrett Smith for their help with mice experiments and preparation of this manuscript, respectively.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, CMMID, 1410 Prices Fork Road, Blacksburg, 24060-0342, VA, USA

    Neeta Jain-Gupta, Ronald Tyler Jr., David L. Caudell & Nammalwar Sriranganathan

  2. Macromolecules and Interfaces Institute, Virginia Polytechnic Institute and State University, Blacksburg, 24061, VA, USA

    Nipon Pothayee, Nikorn Pothayee, Sharavanan Balasubramaniam, Nan Hu, Richey M. Davis & Judy S. Riffle

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  1. Neeta Jain-Gupta
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  2. Nipon Pothayee
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  4. Ronald Tyler Jr.
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  10. Nammalwar Sriranganathan
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Correspondence to Nammalwar Sriranganathan.

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Jain-Gupta, N., Pothayee, N., Pothayee, N. et al. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection. J Nanopart Res 15, 2024 (2013). https://doi.org/10.1007/s11051-013-2024-4

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