The Most Important Element of Blood-Brain Barrier - Case Study Example

Nanoparticle for drug delivery technology to cross blood brain barrier Blood brain barrier (BBB) and protecting the brain Blood-brain barrier (BBB) performs the major function of protecting the brain from varied changes in blood levels, especially changes related to amino acids, ions, peptides and other unknown particles. This barrier is found in the blood capillaries of the brain but is different from other capillaries found in the circulatory system. The cells of the barrier are found to be sealed together tightly, which is also the most important element of this barrier. This helps in preventing substances especially water soluble ones to enter into the brain cells from the blood by passing through the cells. The capillaries are also closed by astrocytic cells that additionally act as a barrier (Zlokovica 2009). Therefore, the only method through which the water soluble substances may permeate BBB is by going through the capillary walls of the brains. However, as the cell membranes of the capillary walls consist of protein/lipid bilayer and also act as BBB. Further, the enzymes found on the cerebral capillaries lining may destroy the peptides as well and other such smaller molecules that are found in the blood and may permeate into the brain (Gabathuler 2010). Old methods of curing brain diseases and associated problems Although, BBB helps in protecting the brain from various infections by acting as a barrier against various disease-inducing practices found in the blood, it also disables water-soluble medicines to reach the brain and treat brain diseases such as tumors and other infections. Most of these infections and diseases uses this defense mechanism of BBB and grows behind BBB to safeguard themselves from the affect of the drugs. In order to solve this problem, researchers for years have been developing drugs that are fat soluble and can cross the BBB. However, such a process of invading the BBB also means helping toxic materials to enter into the cells (Gabathuler 2010). The brain is a rigid structure and requires the volume to remain constant. In such a situation BBB helps in preventing the free water and salts movement from the blood to the brain and thus, keeps the volume constant as well. The BBB controls the secretion of extracellular fluid in the brain, which helps in maintaining the brain volume. However, in case the barrier is breached due to invasion, the salts and water from the blood may enter into the brain and cause swelling or cerebral oedema. This may further result into intracranial pressure, which may cause fatality as well (Gabathuler 2010). Nanoparticle technology for delivering drug Drug delivery by breaching the BBB barrier through nanotechnology has become one of the most researched subjects in clinical neuroscience in the recent past. Nanoparticles may help in performing various tasks in a predefined manner that is also known to be an important element to breach the barrier between the brain and the blood and deliver the drugs to the brain. In the recent times, researches have been conducted in this area to find out about the efficacy of nanoparticle drug delivery in the treatment of central nervous system (CNS) diseases and inhibition of tumors (Silva 2008). Due to the small size of the nanoparticles, they are able to permeate BBB and deliver the drugs through the barrier. In order to conduct this process, many strategies are being used and various combinations of nanomaterials are considered as agents for drug delivery. The use of nanotechnology may also help in reducing the requirement of using invasive procedures for treating brain diseases. This technique would increase the safety of such procedures. Further, active compounds are not needed to carry out this procedure as compared to the process of administrating free drugs. Therefore, active drugs can be modified accordingly to provide maximum benefits. The clinical trials for using nanoparticle technology are still underway and researchers believe it has greater potential in the near future in treating brain diseases in human beings in an efficient manner (Silva 2008). Recent nanoparticles drug delivery procedure to cure brain diseases Researchers at the University of Washington (2009) conducted an experiment wherein they were able to inject fluorescent nanoparticles in the blood and helped it in crossing the BBB barrier in a mouse. The nanoparticles survived for around five days in the tumor of the mouse but did not damage the barrier between the blood and brain. Thus, the experiment was able to find nanoparticles that could permeate BBB without damaging the blood-brain barrier. Similarly, Andrieux and Couvreur (2009) found that nanoparticles based on poly (alkylcyanoacrylates) (PACA) were able to permeate into the brain of healthy animals. They experimented on a CNS disease model as well. They studied the complete passage of the nanoparticles through the BBB through various experiments. Andrieux and Couvreur (2009) stated that some ligands and antibodies may be considered to be good candidates for combining with PACA nanoparticles and help it to permeate through BBB in an easier manner. In another experiment, Liu et al. (2009) proved that nanoparticles are able to cross BBB to suppress the growth of bacteria in Staphylococcus aureus-infected meningitis rabbits. The experiment proved that nanoparticles which were formed through the self-assembling of amphiphilic peptide possess antimicrobial properties which can fight yeasts, bacteria and even fungi. Earlier, the nanoparticles also fought against Staphylococcus aureus infection that affected mice. Thus, Liu et al. (2009) revealed the antimicrobial properties of nanoparticles which may help in treating various brain infections in the near future. Reddy and Labhasetwar (2009) conducted a study to demonstrate that superoxide dismutase (SOD) encapsulated nanoparticles help to reduce brain injury as well promote neurological recovery. They conducted the experiment on a rat with cerebral ischemia. Further, the encapsulated SOD that was delivered in a sustained manner neutralised the impact of reactive oxygen species (ROS) on BBB. Conclusion Bhabra et al. (2009) in a recent paper in Nature Nanotechnology revealed that nanoparticles may have some harmful side effects and can cause cell damages to the blood-brain barrier. The study has raised various questions regarding the safety of such a procedure and using of nanoparticles for drug delivery. The question has become much more potent now as the human trials of this procedure are currently being undertaken. The growing nanoparticles use in drug delivery has certainly raised various concern issues such as whether it is safe to let such particles enter into a crucial part of human body. In their experiments, Bhabra et al. (2009) demonstrated how cobalt-chromium nanoparticles could enter into the brain and cause damage to the fibroblast cells. Some of the other potential disadvantages of using nanoparticle technology are the danger of causing toxicity and poisoning the brain cells. Although, nanoscience might be able to create various improved and new products as well as particles that might be very small, researchers believe such particles may cause health issues for the people who would use them. Further, the field of nanoparticle and its use in drug delivery to the brain is still in the nascent stages and the researchers do not have significant knowledge in this area. The researchers are aware of the technology and how to create particles and materials, but they need to also identify and understand the effect of such a technology and measure the efficacy before emphasising on using such a procedure or conducting large scale researches. Further, without understanding the structure of the nanoparticle, the researchers may create a different material all together which might not be cohesive with the human body and cause additional damages (Zlokovica 2009). Thus, the field of nanoparticles and its use in drug delivery to brain still needs considerable research. However, it has been found that such researches are highly costly and even most pharmaceutical companies are not eager to undertake such an expensive procedure. Also, the success rate of past researches is not that high, which another deterrent is for the researchers and the companies. Further, the high cost of manufacturing and researching such technology would make the procedure commercially unviable (Gabathuler 2010). Reference Andrieux, K. and Couvreur, P. (2009). “Polyalkylcyanoacrylate nanoparticles for delivery of drugs across the blood–brain barrier”. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 1 (5), 463–474. Liu, L. et al. (2009). “Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent”. Nature Nanotechnology 4, 457 - 463. Reddy, M. K. and Labhasetwar, V. (2009). “Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury”. The FASEB Journal 23, 1384-1395. Bhabra et al. (2009). “Nanoparticles can cause DNA damage across a cellular barrier”. Nature Nanotechnology 4, 876 – 883. Gabathuler, R. (2010). “Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases”. Neurobiology of Disease 37 (1), 48-57. Zlokovica, B. V. (2009). “Blood–Brain Barrier and Neurovascular Mechanisms of Neurodegeneration and Injury”. Encyclopedia of Neuroscience, 265-271. Silva, GA (December 2008). "Nanotechnology approaches to crossing the blood-brain barrier and drug delivery to the CNS". BMC Neuroscience 9 (Suppl. 3). University of Washington (2009, August 4). Nanoparticles Cross Blood-brain Barrier To Enable 'Brain Tumor Painting'. ScienceDaily. Read More