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Article | Open Access

Characterization of Monocytes-targeted Nanocarriers Biodistribution in Leukocytes in ex-vivo and in-vivo Models

Einat Cohen-Sela1, Michael Chorny2, Dikla Gutman1, Sivan Komemi1, Nickolay Koroukhov1, Gershon Golomb1( )
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem
Cardiology Research, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104
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Abstract

Aims

On intravenous administration, unprotected nanocarriers are rapidly captured by the mononuclear phagocytic system (MPS). This has been exploited for passive targeting of nanoparticulate drug delivery systems for depleting circulating monocytes and macrophages for the treatment of various disorders. However, the extent of nanocarriers biodistribution among leukocytes, has not been characterized. The aim of this work was to examine the biodistribution of monocyte-targeted nanoparticles and liposomes in leukocytes.

Materials & Methods

Fluorescently-labeled large negative liposomes (LN-LIP, 130±33 nm, -25.2±6.3 mv), large negative NP (LN-NP, 133±40 nm, -40±8 mv), large positive NP (LP-NP, 121±36 nm, +62±9 mv), and small negative NP (SN-NP, 85±26 nm, - 15±2 mv) were formulated. Fluorescence activated cell sorting (FACS) was utilized to determine internalization in rabbit's blood both ex-vivo and in-vivo.

Results & Conclusions

Monocytes, neutrophils, and lymphocytes internalized the NP. SN-NP exhibited the highest selectivity towards monocytes. Granulocytes preferentially internalized LN-LIP in comparison to all polymeric NP formulations. NP charge had no effect on their engulfment by granulocytes, while NP size was found to be an important factor as granulocytes showed preference towards large NP formulations (LN-NP and LP-NP). Lymphocytes preferentially internalized large negatively charged formulations (LN-LIP and -NP). The ex-vivo results failed to predict in-vivo results. Formulations targeted to monocytes distribute into other leukocytes as well, which should be determined in-vivo.

Keywords

LiposomesEndocytosisNanoparticles (NP)UptakeInternalizationMonocytesLeukocytes

Electronic Supplementary Material

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Nano Biomedicine and Engineering
Volume 2 Issue 2,
June 2010
Pages 91-99
DOI: 10.5101/nbe.v2i2.p91-99
Cite this article:
Cohen-Sela E, Chorny M, Gutman D, et al. Characterization of Monocytes-targeted Nanocarriers Biodistribution in Leukocytes in ex-vivo and in-vivo Models. Nano Biomedicine and Engineering, 2010, 2(2): 91-99. https://doi.org/10.5101/nbe.v2i2.p91-99

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Received: 02 May 2010
Accepted: 06 June 2010
Published: 26 June 2010
© 2010 E. Cohen-Sela et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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