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Role of Cell Interactions of PLG Nanoparticles in the Drug Delivery Lifecycle
Mendeleev University of Chemical Technology of Russia
The pharmacokinetics of nano-delivery systems is mostly evaluated by their plasma
concentration-time profiles. At the same time, the blood partitioning behavior of the widely
used PLG nanoparticles (PLG NP) indicates that a significant fraction is bound to the blood
cells, resulting in misinterpretation of the nanoformulation pharmacokinetics (1).
In the present study the NP – blood cell interactions over time and the role of immune cells in
the PLG NP extravasation and tumor delivery was investigated using the intravital microscopy
(IVM). The doxorubicin-loaded PLG NP (PLG-Dox NP) with different drug release rates (fast-,
medium- and slow-releasing formulations) were prepared by a homogenization - solvent
evaporation technique. The fluorescent label (Cy5) was covalently attached to the polymer
allowing visualization of both NP and Dox. Visualization of the NP delivery to the
subcutaneous 4T1 tumor in mice was performed by IVM (Nikon A1R MP). The NP uptake by
subpopulations of immune cells was further investigated by flow cytometry.
The extravasation through the tumor vessel wall via the macro- and microleakages were
detected for all NP types, enabling Dox delivery to the cell nuclei. The unspecific adsorption
of the NP to the blood cells followed by their redistribution to the monocytes and neutrophiles
was observed starting from 15 min after injection and was increasing with time (uptake by
neutrophils was 1.5% to 25% after 15 and 30 min, respectively). Thus, the NP uptake by immune cells appears to be an additional phase in the nanoparticle drug delivery lifecycle.
1. Kovshova T, et al. Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin. Molecules 2021; 26(4): 831. doi.org/10.3390/molecules26040831
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