Researchers found a way to remove nanoparticles from blood

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood brain barrier { which is a highly selective permeability fencing that separates the circulating blood from the brain extracellular fluid in the central nervous system consisting of the brain and the spinal cord. The blood–brain barrier is formed by brain endothelial cells, which are connected by tight junctions with an extremely high electrical resistivity of at least 0.1 Ω⋅m The blood–brain barrier allows the passage of water, some gases, and fat-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function. On the other hand, the blood–brain barrier may prevent the entry of lipophilic, potential neurotoxins by way of an active transport mechanism mediated by P-glycoprotein. Astrocytes -  characteristic star-shaped glial cells   in the brain and spinal cord - are necessary to create the blood–brain barrier. A small number of regions in the brain do not have a blood–brain barrier. The blood–brain barrier occurs along all capillaries - any of the fine branching blood vessels that form a network between the arterioles and venules - and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or hydrophilic (those attracted to water) molecules into the cerebrospinal fluid of the central nervous system, while allowing the diffusion of small hydrophobic (those that are repelled by water) molecules (O₂, CO₂, hormones). Cells of the barrier actively transport metabolic products such as glucose across the barrier with specific proteins. ^} using nanoparticles ( particles between 1 and 100 nanometers in size. In nanotechnology, a particle is defined as a small object that behaves as a whole unit with respect to its transport and properties). These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression and brain tumours.  Part of the difficulty has been solved with the use of nanotechnology in finding cures for these central nervous system diseases.

Nanotech Marvels ( Art work by Dr. Krishna Kumari Challa)

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The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly in the future. At present many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. Besides the potential beneficial use also attention is drawn to the questions how one should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed. One aspect that is bothering the medical fraternity is how to remove these nano particles from blood once their work has been done. And here is some good news for them.

Now a new technology that uses an oscillating electric field to easily and quickly isolate drug-delivery nanoparticles from blood was developed by the engineers at the University of California, San Diego. The technology could serve as a general tool to separate and recover nanoparticles from other complex fluids for medical, environmental, and industrial applications.

Nanoparticles, which are generally one thousand times smaller than the width of a human hair, are difficult to separate from plasma, the liquid component of blood, due to their small size and low density. Traditional methods to remove nanoparticles from plasma samples typically involve diluting the plasma, adding a high concentration sugar solution to the plasma and spinning it in a centrifuge, or attaching a targeting agent to the surface of the nanoparticles. These methods either alter the normal behavior of the nanoparticles or cannot be applied to some of the most common nanoparticle types.

"This is the first example of isolating a wide range of nanoparticles out of plasma with a minimum amount of manipulation," said Stuart Ibsen, a postdoctoral fellow in the Department of NanoEngineering at UC San Diego and first author of the study published October in the journal Small. "We've designed a very versatile technique that can be used to recover nanoparticles in a lot of different processes."

This new nanoparticle separation technology will enable researchers -- particularly those who design and study drug-delivery nanoparticles for disease therapies -- to better monitor what happens to nanoparticles circulating in a patient's bloodstream. One of the questions that researchers face is how blood proteins bind to the surfaces of drug-delivery nanoparticles and make them less effective. Researchers could also use this technology in the clinic to determine if the blood chemistry of a particular patient is compatible with the surfaces of certain drug-delivery nanoparticles.

The device used to isolate the drug-delivery nanoparticles was a dime-sized electric chip manufactured by La Jolla-based Biological Dynamics, which licensed the original technology from UC San Diego. The chip contains hundreds of tiny electrodes that generate a rapidly oscillating electric field that selectively pulls the nanoparticles out of a plasma sample. Researchers inserted a drop of plasma spiked with nanoparticles into the electric chip and demonstrated nanoparticle recovery within 7 minutes. The technology worked on different types of drug-delivery nanoparticles that are typically studied in various labs.

The breakthrough in the technology relies on designing a chip that can work in the high salt concentration of blood plasma. The chip's ability to pull the nanoparticles out of plasma is based on differences in the material properties between the nanoparticles and plasma components. When the chip's electrodes apply an oscillating electric field, the positive and negative charges inside the nanoparticles reorient themselves at a different speed than the charges in the surrounding plasma. This momentary imbalance in the charges creates an attractive force between the nanoparticles and the electrodes. As the electric field oscillates, the nanoparticles are continually pulled towards the electrodes, leaving the rest of the plasma behind. Also, the electric field is designed to oscillate at just the right frequency: 15,000 times per second.

Source: Research reports of University of California - San Diego