Nanoparticles don't get into the brain? Lubricate with polyethylene glycol!
The polyethylene glycol coating increases the ability of nanoparticles to diffuse into brain tissue
LifeSciencesToday by materials Phys.Org : Polymer coating allows nanoparticles to diffuse through the brainAmerican scientists have found a way to increase the ability of nanoparticles of a larger size than before to diffuse into brain tissue.
Such nanoparticles may become a new means of drug delivery for targeted treatment of diseases such as brain tumors and stroke.
The problem scientists face when trying to deliver nanoparticles to the brain is that the substance filling the space between brain cells has a high viscosity and its properties are close to mucus. The spread of nanoparticles larger than 64 nanometers in an environment with such properties is sharply limited. This makes it difficult to use most nanotechnological delivery vehicles, since nanoparticles of the required size cannot effectively penetrate the brain tissue.
Trying to find a way to deliver larger nanoparticles, scientists at Johns Hopkins University School of Medicine, led by Elizabeth Nance and Justin Hanes, PhD, experimented with nanoparticles of various sizes and with different coatings. The solution was found when scientists tightly coated the nanoparticles with polyethylene glycol (PEG). PEG-coated nanoparticles with a size of 114 nm actively spread through the tissue of the newly deceased human brain. These results were confirmed in experiments with particles up to 100 nm in size on the brains of live mice and on rat brain samples.
Left: Polyethylene glycol-coated nanoparticles (green) penetrate into the normal brain of a rodent. Without PEG coating, negatively charged hydrophobic particles (red) of the same size cannot penetrate the brain tissue.
On the right: green-illuminated PEG-coated nanoparticles can move through channels and areas between brain cells, shown as dark rounded spots. Nanoparticles also coated with PEG, but much larger (red) are retained by cells and components of the extracellular environment of the brain.
Photo: Elizabeth Nance, Graeme Woodworth, Kurt Sailor.
Polyethylene glycol is a low–toxic polymer with a wide range of applications, including as a dispersant in toothpastes and skin creams and an anti-foaming agent in food products. As a coating for nanoparticles, PEG protects nanoparticles from hydrophobic and electrostatic interactions with tissues and prevents them from sticking to brain cells. With a diameter of more than 114 nm, the particles begin to stick to the cells, but Dr. Haines believes that the maximum size of nanoparticles can reach 200 nm, since this is the size of the pores in the intercellular environment of the brain.
The penetration of larger nanoparticles into the brain is expected to make the delivery of drugs more uniform, long-lasting and effective. Such nanoparticles can be used in the treatment of brain tumors, stroke, neuroinflammation and other brain diseases in which the blood-brain barrier is damaged or local delivery strategies may be used.
However, the researchers believe that additional studies should be conducted prior to the start of clinical trials in order to obtain information about possible undesirable side effects or toxicity of drug-loaded nanoparticles.
The results of the study are published in the journal Science Translational Medicine:
Nance et al., A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue.
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