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.

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.

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.