Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo

Title:Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo

Volume: 14 Issue: 8

Author(s): Resham Chhabra, Barbara Ruozi, Antonietta Vilella, Daniela Belletti, Katharina Mangus, Stefanie Pfaender, Tasnuva Sarowar, Tobias Maria Boeckers, Michele Zoli, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi and Andreas Martin Grabrucker

Affiliation:

Keywords: Blood brain barrier, brain, drug delivery, Nanoparticle (NP), Poly(D, L-lactide-co-glycolide) (PLGA), Zn²⁺, ZnSO₄.

Abstract: A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson’s and Alzheimer’s disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. However, given the restriction of zinc uptake into the brain by the blood-brain barrier, methods for controlled regulation and manipulation of zinc concentrations within the brain are rare. Here, we performed in vivo studies investigating the possibility of brain targeted zinc delivery using zinc-loaded nanoparticles which are able to cross the blood-brain barrier. After injecting these nanoparticles, we analyzed the regional and time-dependent distribution of zinc and nanoparticles within the brain. Moreover, we evaluated whether the presence of zinc-loaded nanoparticles alters the expression of zinc sensitive genes and proteins such as metallothioneins and zinc transporters and quantified possible toxic effects. Our results show that zinc loaded g7 nanoparticles offer a promising approach as a novel non - invasive method to selectively enrich zinc in the brain within a small amount of time.

Cite this article as:

Chhabra Resham, Ruozi Barbara, Vilella Antonietta, Belletti Daniela, Mangus Katharina, Pfaender Stefanie, Sarowar Tasnuva, Boeckers Maria Tobias, Zoli Michele, Forni Flavio, Vandelli Angela Maria, Tosi Giovanni and Grabrucker Martin Andreas, Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo, CNS & Neurological Disorders - Drug Targets 2015; 14 (8) . https://dx.doi.org/10.2174/1871527314666150821111455