Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo

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.

Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an injury

“…Major strategies for functionalization of biomaterial matrices are based on the delivery of growth factors (GFs) or other small bioactive molecules [ 30 , 31 ]. However, scarce reports describe material systems for ion-delivery to stimulate intracellular signaling [ [32] , [33] , [34] , [35] ]. Still, there is a need to develop new methods and materials, which promote skeletal muscle repair and functional regeneration.…”

The Role of Trace Metals in Alzheimer’s Disease

“…This system has been considered as a Trojan horse strategy to effectively deliver Zn to the brain with a low-toxicity profile (129). Three hours after ip injection of NPs, an increase of Zn levels in the brain and the increase of zinc-sensitive genes such as MT and Zn transporters were seen (130). The same pharmacological approach applied to APP23 mice, an animal model of AD, showed promising effects such as Aβ dis-aggregation, a reduction of inflammation, and synapse stabilization (129).…”

Prospects of Zinc Supplementation in Autism Spectrum Disorders and Shankopathies Such as Phelan McDermid Syndrome

“…The type of supplement needs to ensure effective zinc uptake, but also zinc delivery into the brain. Here, recently developed nanoparticles delivering zinc across the BBB may be promising (Chhabra et al, 2015 ; Vilella et al, 2017 ). Additionally, the standard laboratory diet for Shank mouse models has to be carefully controlled for zinc content.…”