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Brain Disorders: Blood Brain Barrier Essay

3422 words - 14 pages

Brain disorders are major concern of modern world in terms of economic liability and human suffering with the increased number of aged population as a result of the long life expectancy. The main challenge in the treatment of many of the neurodegenerative diseases is the presence of a polarized layer of endothelial cells that comprises the blood–brain barrier (BBB) which precludes access of systemically administered medicines to brain tissue. Currently more than 98% of all small molecules and 100% of large-molecule pharmaceutics do not cross the blood brain barrier unless it is disrupted or loosened due to any of the diseased conditions .1a As a result, effective therapy becomes possible only at a later stage of the disease when the integrity of the barrier is compromised. BBB also restricts early diagnosis of the diseases as the imaging contrast agents are prevented from entry.1b-e However, despite the tight protection given to the brain, BBB allows selective transport of essential nutrients and oxygen to the brain. Specific membrane transport proteins are relatively higher in BBB which allows the entry of essential nutrients, such as glucose and certain amino acids or related molecules, including L-DOPA. Certain receptors present on BBB also allows the entry of macro molecules into the brain through receptor mediated pathways.1f-h These pathways may be explored for an effective delivery of imaging moiety or drug to the brain facilitating early diagnosis and effective therapy.
Nano sciences and technology opens a wide door to traverse through the BBB at an early stage due to extremely small size and size dependent optical, electrical and magnetic properties.2 Previous studies in this direction have used dendrimer, quantum dots, iron oxide, gold, titanium, siloxane, polymeric nanoparticles etc. as carriers of drugs or they served as imaging moieties in conditions like brain tumor and brain related disorders. In many of the above studies easy entry of the nanoparticles was facilitated either by leaky BBB in the case of brain tumor or by the effect of TAT peptides, lactoferrin etc conjugated to the nanoparticles. 2c-j Herein we report the use of gold cluster of very small size to target the brain, in the early stages of disease, when the barrier is not much distorted.
We have developed a glutathione stabilized gold cluster (GQC) with very small size of the order of 0.7 nm and tuned its emission around 750 nm to enable the fluorescence imaging of the particles as they enter the BBB. Gold based nanocarriers dominate over other nanomaterials because of its size tunable optical property and non toxicity.3 Among the various size and shape of gold nanomaterials, gold clusters have got wide attention in the field of bio imaging due to its inherent fluorescence emission.3f-j Recent reports on the use of gold clusters include cell labeling, diagnosis and sensing applications. 4 Little efforts have been made to study the blood brain barrier...

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