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Nanomaterials Cross the Brain Side of the Blood-Brain Barrier Model

A new study discloses that nanomaterials found in healthcare and consumer products can pass from the bloodstream to the brain side of a blood-brain barrier model with differing ease based on their shape — thereby causing possible neurological impacts that could be both positive and negative.

Nanomaterials Cross the Brain Side of Blood-Brain Barrier Model
Nanomaterials can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape. Image Credit: University of Birmingham.

Researchers discovered that metal-based nanomaterials like zinc and silver oxide can cross an in vitro model of the “blood-brain barrier” (BBB) as both dissolved ions and particles — thus adversely influencing the health of astrocyte cells, which help regulate the neurological responses.

However, the scientists also consider that their breakthrough will help design safer nanomaterials and could pave the way to target hard-to-reach locations while treating brain disease.

An international group of scientists found that the physicochemical properties of metallic nanomaterials impact their effectiveness at intruding into the in vitro model of the blood-brain barrier and their possible levels of toxicity in the brain. They have published the study results in the journal PNAS.

Some shapes of zinc oxide and silver nanomaterials in higher concentrations might impair cell growth and cause higher permeability of the BBB, which can result in the BBB permitting simpler brain access to such compounds.

In brain health, the BBB plays a crucial role by limiting the path of several chemical substances and foreign molecules into the brain from surrounding blood vessels. Impaired BBB integrity compromises the health of the central nervous system and higher permeability to foreign substances might ultimately result in brain damage (neurotoxicity).

We found that silver and zinc oxide nanomaterials, which are widely used in various daily consumer and health-care products, passed through our in vitro BBB model, in the form of both particles and dissolved ions.

Iseult Lynch, Study Co-Author and Professor of Environmental Nanosciences, University of Birmingham

Variation in shape, size and chemical composition can dramatically influence nanomaterials penetration through the (in vitro) blood-brain barrier. This is of paramount importance for tailored medical application of nanomaterials — for example, targeted delivery systems, bioimaging and assessing possible risks associated with each type of metallic nanomaterial,” added Lynch.

The BBB is a physical barrier consisting of a tightly packed layer of endothelial cells that surrounds the brain and isolates the blood from the cerebrospinal fluid, thereby enabling the transfer of oxygen and essential nutrients but avoiding the access of a majority of the molecules.

Latest studies discovered that nanomaterials like zinc oxide can collect on the brain side of the in vitro BBB in modified states, which could have an impact on brain health and neurological activity. Ingested, inhaled and dermally applied nanomaterials could reach the bloodstream and a small part of these might cross the BBB, eventually affecting the central nervous system.

A library of metallic nanomaterials with different particle shapes, sizes and compositions was synthesized by the researchers, thereby assessing their potential to enter the BBB, with the help of an in vitro BBB model, followed by an evaluation of their fate and behavior in and beyond the model BBB.

Understanding these materials’ behavior once past the blood-brain barrier is vital for evaluating the neurological effects arising from their unintentional entry into the brain. Neurotoxicity potential is greater in some materials than others, due to the different ways their shapes allow them to move and be transported.

Zhiling Guo, Study Co-Author and Research Fellow, University of Birmingham

The researchers examined mixed sizes of iron oxide and cerium oxide, together with zinc oxide and four different shapes of silver — nanowires (Ag NW), rod-shaped (Ag NR), disc-like (Ag ND) and spherical (Ag NS).

Zinc oxide easily breached the in vitro BBB. The scientists discovered that disc-like and spherical silver nanomaterials experienced various dissolution regimes. This helps slow the conversion of silver-sulfur compounds inside the BBB, thereby making “easier” entry pathways.

Zinc oxide has been utilized as a colorant and a bulking agent. In over-the-counter drug products, it is utilized as a skin protectant and a sunscreen that helps reflect and scatter UV radiation to help decrease or avoid premature aging of the skin and sunburn. Silver finds use in skincare and cosmetic products like anti-aging creams.

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