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Biodistribution of rhodamine B fluorescence-labeled cationic nanoparticles in rats

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Abstract

We investigated the biodistribution following the administration of nanosized (about 50 and 90 nm) cationic (ζ: +30 and +50 mV) micelles and liposomes intended for drug delivery. The particles were stable and well characterized with respect to size and ζ potential. Ten 5- to 6-week-old male rats were used. The animals were randomly allocated to five groups receiving either cationic micelles or cationic liposomes by single intravenous (IV) administration at a dose of 100 mg/kg bodyweight by single intracerebroventricular (ICV) injection at a dose of 50 μg or no treatment. ICV administration was used to study local distribution in the brain and IV administration to study the systemic distribution of the particles. For both types of particles, ICV administration showed distribution in all ventricles in the brain while IV delivery displayed distribution to the major organs liver, spleen, kidney and lung, but not to the brain. Our data suggest that cationic micelles and liposomes are widely distributed in the body, indicating that these could potentially be used as drug delivery carriers to the major organs, but they do not cross the blood–brain barrier to a significant extent, without a targeting ligand attached. However, they are able to persist in the ventricles of the brain up to 24 h after ICV administration, demonstrating a new ability.

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Acknowledgments

The excellent assistance of the Animal Facility, Section of Neurobiology and Section of Pathology and Clinical Pathology at H. Lundbeck A/S, Pramod Kumar EK and Jonas Rosager Henriksen from DTU Nanotech and the contribution from DHI are gratefully acknowledged. This work was supported by H. Lundbeck A/S, DHI and Faculty of Health and Medical Sciences, University of Copenhagen.

Conflict of interest

The authors declare no conflicts of interest that could influence the present study.

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Author notes

  1. Kristina Bram Knudsen

    Present address: National Research Center for the Working Environment, Copenhagen, Denmark

Authors and Affiliations

  1. Faculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 9, 1, 1870, Frederiksberg C, Denmark

    Kristina Bram Knudsen & Jens Lykkesfeldt

  2. H. Lundbeck A/S, Valby, Denmark

    Kristina Bram Knudsen, Helle Northeved & Karen Malene Wegener

  3. Center for Nanomedicine and Theranostics, DTU Nanotech, Technical University of Denmark, Lyngby, Denmark

    Torben Gjetting & Thomas L. Andresen

  4. DTU FOOD, Technical University of Denmark, Søborg, Denmark

    Anders Permin

  5. Environment and Toxicology, DHI, Hørsholm, Denmark

    Henrik Rye Lam

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  1. Kristina Bram Knudsen
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Correspondence to Jens Lykkesfeldt.

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Knudsen, K.B., Northeved, H., Gjetting, T. et al. Biodistribution of rhodamine B fluorescence-labeled cationic nanoparticles in rats. J Nanopart Res 16, 2221 (2014). https://doi.org/10.1007/s11051-013-2221-1

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