Research Summary: Development of Novel Zn2+ Loaded Nanoparticles Designed for Cell-Type Targeted Drug Release in CNS Neurons: In Vitro Evidences

ABSTRACT

Intact synaptic function and plasticity are fundamental prerequisites to a
healthy brain. Therefore, synaptic proteins are one of the major targets for
drugs used as neuro-chemical therapeutics. Unfortunately, the majority of drugs
is not able to cross the blood–brain barrier (BBB) and is therefore
distributed within the CNS parenchyma. Here, we report the development of novel
biodegradable Nanoparticles (NPs), made of poly-lactide-co-glycolide (PLGA)
conjugated with glycopeptides that are able to cross the BBB and deliver for
example Zn2+ ions. We also provide a thorough characterization
of loaded and unloaded NPs for their stability, cellular uptake, release
properties, toxicity, and impact on cell trafficking. Our data reveal that these
NPs are biocompatible, and can be used to elevate intracellular levels of
Zn2+. Importantly, by engineering the surface of NPs with
antibodies against NCAM1 and CD44, we were able to selectively target neurons or
glial cells, respectively. Our results indicate that these biodegradable NPs
provide a potential new venue for the delivery Zn2+ to the CNS
and thus a means to explore the influence of altered zinc levels linked to
neuropsychological disorders such as depression.

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Publisher: Public Library of Science

Date Published: 23-March-2011

Author(s): Grabrucker A., Garner C., Boeckers T., Bondioli L., Ruozi B., Forni F., Vandelli M., Tosi G.

Link: https://doi.org/10.1371/journal.pone.0017851

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