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Nanotechnology improves the prospect of better treatment for brain disorders |
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Jan 07, 2008 at 09:56 AM |
1,300 to 1,400 grams and several thousand kilometers of about 100 billion interconnected nerve cells control every movement, thought, sensation, and emotion that comprise the human experience. Within the brain and spinal cord there are ten thousand distinct varieties of neurons, trillions of supportive cells, a few more trillion synaptic connections, a hundred known chemical regulating agents, kilometers of minuscule blood vessels, and untold mysteries of how - almost flawlessly - all these components work together. This is the amazing brain (source: BrainSource.com). Given the incredible complexity of the brain, it doesn't come as a big surprise that a lot of things can go wrong.
The A-Z of brain disorders is a very long list. Several of these disorders (such as Parkinson and Alzheimer disease, but also schizophrenia, epilepsy, and bipolar disorder), not to mention tumors, are so severe that they require treatment of the brain. But even when there are promising pharmaceutical compounds for their treatment, more than 98% of these potential agents do not reach the drug development stage. The reason is the blood-brain barrier (BBB), a tight seal of endothelial cells lines the blood vessels in the brain and acts as a barrier to protect its cells. BBB strictly limits transport into the brain through both physical (tight junctions) and metabolic (enzymes) barriers and keeps most substances, such as chemicals and large biomolecules, out of the brain. The combined use of peptides and nanotechnology offers tremendous hope in the treatment of brain disorders by offering a way for drugs (the therapeutic kind) across the BBB.
The challenge in treating most brain disorders is overcoming the difficulty of delivering therapeutic agents to specific regions of the brain by crossing the BBB. The problem is that the BBB does not differentiate what it keeps out. With very few exceptions, only non-ionic and low molecular weight molecules soluble in fat clear the BBB. For instance, alcohol, caffeine, nicotine and antidepressants meet these criteria. However, large molecules needed to deliver drugs do not.
In a recent review in the Journal of Peptide Science, Dr. Ernest Giralt from the Institute for Research in Biomedicine in Barcelona, Spain, together with Dr. Meritxell Teixidó from his group, summarized literature reports on the use of peptides and nanotechnology for the treatment and diagnosis of brain disorders, and comparing these approaches to other methods ("The role of peptides in blood-brain barrier nanotechnology").
"Over the past few decades, pharmaceutical technology has lead to the emergence of different nanosystems or nanoplatforms tailored to deliver drugs to the brain, including polymeric nanoparticles, liposomes, and solid lipid nanoparticles" Giralt tells Nanowerk.
In their review, Teixidó and Giralt focus on the use of polymer matrix nanoparticles. These are solid colloidal particles which can carry therapeutic drugs or diagnostic agents complexed by adsorption, entrapment, or covalent attachment. The nanoscale of the particle may improve the transport properties and stability of the transported agent. Once the nanoparticle reaches the desired target, release can be achieved by one or more mechanisms such as desorption, diffusion, and nanoparticle erosion.
Two nanoparticle applications are most promising for brain research and disorder treatment: the transport of MRI contrast agents to the brain to enable studying the central nervous system of patients; and for improved drug delivery across the BBB.
"One of the most promising, yet challenging, applications of nanoparticles is the delivery of therapeutic peptides and proteins to the brain" says Giralt. "The main concern during the loading of nanoparticles with peptides or proteins is the chemical stability of the peptide or protein to the elevated temperatures, shear force, surfactants, free radicals, and UV radiation implied. Moreover, the function of proteins depends on their structure. Hence, the preparation needs to be optimized for each nanoparticle formulation."
Read More: Nanowerk
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