This study will be a randomized control study that will aim at evaluating the effects of nanoparticles found in nanotechnology drugs. Nanotechnology drugs have been shown to have positive effects on the human body but with some adverse effects which have not been exploited. This study will therefore specifically evaluate the effects of nanotechnology drugs with reference to Abraxane which is used in the treatment of cancer. The hypothesis of the study is that nanoparticles found in nanotechnology drugs have adverse effects on brain activity which include brain electrical activity and morphology. The study will involve the use of 40 study subjects and 20 control subjects who have been diagnosed with breast cancer. Electroencephalography will be used to monitor brain electrical activity over a duration of six months and taking of CT-scans of the brain. This will involve subjects in both groups. These will help in monitoring changes in the electrical activity of the brain and any morphological or structural changes caused as a result of the nanoparticles found in nanotechnology drugs. This study is will be of great assistance to both manufacturers and consumers of nanotechnology drugs as the adverse effects these nanotechnology drugs have on the brain will be highlighted. The results of this study will highlight the adverse effects that will open up a window for more research studies to be carried out.
Nanotechnology, according to the National Nanotechnology Initiative (NNI) is the study of structures that are about 100 nanometers or even less. When particles get this small, their physics change, and the ratio of surface atoms to their total number increases significantly meaning that they possess highly increased surface area and surface reactivity. Electrical, magnetic, optical, and biological properties are also changed. The application of nanotechnology in pharmacy means that drugs containing nano-sized active particles, breakthrough drug delivery systems hence allowing deposition of medications in previously inaccessible areas of the body, and improved methods of diagnosis and medical devices (Heide, 2008). Nanoparticles are known to have adverse effects on both the environment and the human body. Some of the products that have been known to have nanoparticles are the sunscreens that contain nanoparticles of zinc oxide and titanium dioxides which are not disclosed by manufacturers as this is not a requirement currently as there are no regulations on nanoparticles contained in sunscreens. Several studies have shown that these two chemicals have the ability to create free radicals, which can cause tissue damage even at the smallest tissue (Heide, 2005). The Food and Drug Administration’s role in regulating nanotechnology in the drug is not well understood although it has already approved some drugs that may contain nanoparticles.
Table 1: FDA approved products utilizing nanotechnology
|Megace ES||Par Pharmaceuticals||Appetite stimulant/ Elan’s Nano Crystal technology||July 2004|
|Abraxane||APP||Breast cancer/ albumin-bound paclitaxel||January 2005|
|Doxil||Alza Corporation||Ovarian cancer and kaposi’s sarcoma/ STEALTH technology||February 2005|
|Emend||Merck & Co.||Antiemetic for chemotherapy/Elan’s Crystall technology||March 2003|
|TriCor||Abbott Laboratories||Cholesterol-lowering/Elan’s Nano Crystal technology||December 2004|
|Estrasorb||Novavax, Inc||Severe vasomotor symptoms/Novavax’s micellar nanoparticles drug-delivery platform||October 2003|
|Rapamune||Wyeth||Immunosuppressant/Elan’s Nano Crystall technology||August 2000|
|Articoat||Smith & Nephew||Antimicrobial dressing/Silver containing SILCRYST Nanocrystals||May 2005|
|SilvaGard||AcryMed, Inc||Antimicrobial (silver) surface treatment/SilvaGard||December 2005|
|Zirconiumoxide||Altair Nanotechnologies, Inc||Dental applications/Nano sized zirconiumoxide is strong and transparent to light, but opaque to x-rays.||September 2003|
One of the fundamental questions that need to be addressed is “what are the effects of nanoparticles on the brain and other body organs?” drugs manufactured using nanotechnology possesses nanoparticles that have the capability to cross the blood-brain barrier and their effects on the brain is not yet known. This study will therefore seek to identify the effects of nanoparticles found in drugs manufactured using nanotechnology. This is an area that has not been extensively researched and therefore more clinical studies need to be done. Nanoparticles can migrate and accumulate in body organs such as the liver, kidney, and brain where they can cause damage. Other studies have also shown that titanium dioxide nanoparticles which are widely used in the manufacture of paints, cosmetics, and sunscreens are able to move via the nose of mice to the brains where they destroy the neurons. It is worth noting that nanomedicine and nanotechnology in general, is a new field with no experimental data about its adverse effects on the human body. Its toxicities on the brain have not been explored. A study carried out by Thomas A. Faunce (pp.189-191) titled “Nanotherapeutics: new challenges for safety and cost-effectiveness regulation in Australia” revealed that there are several loopholes in the regulation of the use of nanotechnology in the pharmaceutical industry with a large gap on available data on safety measures. This study shows that the safety of nanotechnology in medicine pharmacy is far from being realized. A study by Kreuter (p. 4) titled “Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles)” showed that nanoparticles formulations aided the transport of hexapeptide dalargin to cross the blood-brain barrier. The intravenous injection of the complex consisting of nanoparticles and the drug resulted in analgesics effects with the controls not exhibiting any effects. The study further reported that the complex crossed the brain barrier through phagocytic uptake of the complex by brain blood vessels endothelial cells. This study confirms that nanoparticles are capable of crossing the blood-brain barrier.
In another study carried out by Jiangxue (pp. 72-80) that aimed at evaluating the Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases reported accumulation and toxicity results in vivo of two crystalline phases of TiO2 nanoparticles. (80 nm, rutile and 155 nm, anatase; purity >99%). After carrying out the procedures in the study, pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain was analyzed. Morphological changes in the brain were also observed. The study showed that there were morphological changes, oxidative stress occurred in the whole brain. The findings indicated that anatase TiO2 nanoparticles exhibit higher worry on some tested biological effects. The study concluded that nasal instilled TiO2 nanoparticles could be transported into the central nervous system where they can cause potential lesions of the brain and specifically in the hippocampus. This study, therefore, has proved the fact that nanoparticles can migrate from other body parts and organs into the brain from which they can cause adverse effects. This study and others have been carried out using non-human subjects and mostly mice.
The objective of this study will be to evaluate the effects of nanoparticles found in nanotechnology drugs on the brain. The mechanisms by which the nanoparticles pass through the blood-brain barrier (BBB) will be explained. The study will also strive to find out which parts of the brain are affected by the nanoparticles, how the nanoparticles cross the BBB, how the nanoparticles interact with chemicals found in the brain or how they cause damage to the brain tissues, and eventually how these nanoparticles can be removed from the brain. The understanding of these objectives will explain the effects of drug nanoparticles on brain activity. These objectives will be met through a randomized control study where voluntary subjects will be used. Volunteers will include both study subjects who will be currently on a particular drug manufactured by nanotechnology and has nanoparticles while the controls will be volunteers who will be on a drug that has not been manufactured using nanotechnology. Both study groups will be patients who will have already been diagnosed with cancer between stages I and II. The study subjects will then be followed over a period of 6 months. At the beginning of the study, the subjects’ brain electrical activity of the brain will be evaluated and recorded using electroencephalography (EEG). The brains’ electrical activity will be evaluated on a monthly basis at regular intervals for both the control group and the study group. At the end of the 6 months, the two groups will be finally evaluated and the monthly evaluation reports will be scrutinized so that any changes from the initial brain activities that were evaluated before the start of the study. It will be right to state that this study does not and will not introduce a new drug into the market but will aim at following patients who are on a drug that is approved by the FDA and has been in use since 2005.
In this study, two methods will be employed to find the effects of nanoparticles from nanotechnology drugs on the brain’s activity and structures. The first method will involve imagery studies whereby computed topography scan (CT-scan) will be taken from each and every participant. This will be taken at the beginning of the study. The main objective of this method will be to know the status of the brain structures and morphology before the commencement of nanotechnology drug therapy. Another set of images will be taken every month until the six months end. Differences in structures and morphology of brain structures in the CT scans of each and every patient will then be studied and evaluated in order to detect any changes in brain morphology or damages to brain structures. This will help in detecting the damages caused by nanoparticles found in nanotechnology drugs.
The second method will involve the evaluation of brain electrical activities using electroencephalography (EEG). These activities will be evaluated at the beginning of the study, and then after every month, and finally at the 6th month. This will enable the researcher to detect any changes in the brain’s electrical activity that will have been caused by nanoparticles found in nanotechnology drugs. The study subjects will involve two groups, that is, the study subjects and control subjects. Both groups will be gotten through a recruitment drive from local hospitals with cancer units and or health institutions specialized in cancer therapy. The subjects will be those diagnosed with breast cancer, stage I and II. The subjects will not be receiving any form of therapy at the time of recruitment. In both groups, the subjects will be between the age of 28 and 45 years of age with the sex ratio of females to males in both study groups being 2 to 3. The total sample size for the study will be 60 subjects of which 40 will be study subjects and 20 control subjects. The drugs to be used by the study subjects are an anticancer drug that has been manufactured through nanotechnology and have been approved by the FDA. In this case, the study will use Abraxane which was approved by the FDA in January 2005 and is used in the treatment of breast cancer. The prescription of this drug to the patients will be by the physicians working in these hospitals and at no given time will be influenced by this study. The drugs will be availed to the study subjects at no cost. The control subjects will be those using other cancer drugs and not Abraxane. These two methods will involve research assistants who will include radiographers, physicians, psychologists, supportive staff and data analysts. The study will involve three major phases which are: the recruitment phase which will basically involve recruitment of the study subjects, the execution phase which will involve implementing the study and finally the last phase that will involve the analysis of and interpretation of data. Discussion and Conclusion As mentioned above, this study will be aiming at determining the effects of nanoparticles found in nanotechnology drugs used in the treatment of breast cancer. Despite the fact that nanoparticles have physiologic safety considerations, other practical safety issues need to be considered for purposes of protecting the patient and health care professionals. This therefore will place the need for the development of detailed handling and administration protocols for the safe use of nanoparticles as more studies have proved that nanoparticles can cause multiple adverse effects which include non-specific CNS effects translocation from the lungs to the circulation and even localized and systematic inflammatory responses (Born, p. 115).
One of the studies that looked at applications and hazards of nanoparticles titled “Drug delivery and nanoparticles: applications and hazards” by De Jong and Borm, (p.49) had results that were both showed nanoparticles have both positive and negative effects. They appreciated the fact nanotechnology is set to spread rapidly. The two authors provided an overview of systems that are currently used in drug delivery. They reported that more attention should be drawn towards the lessons learned from nanoparticles toxicities and that current requirements may be adequate to detect most of the adverse effects of nanoparticles formulations, it cannot be expected that all aspects of nanoparticles toxicology will be detected. They, therefore, concluded that more additional specific testing is needed. The findings of this study demonstrate the need to carry out the study of nanoparticles’ effects on brain activities.
This study tends to evaluate the effects of nanoparticles on brain function and morphology. These study results are likely to prove that nanoparticles found in nanotechnology drugs have adverse effects on brain function and brain morphology. Just as other earlier studies that were carried out using mice show that nanoparticles have adverse effects on the brain/CNS, this study will confirm the same on human beings. As earlier mentioned, this study will use a drug that has been approved by FDA and will just follow up patients who will be on the drug Abraxane. These results will have serious implications for my study as a new doubt on the safety of and efficacy of nanotechnology drugs more so those that have already been approved by the FDA will be questioned. The FDA’s ability to monitor and regulate nanotechnology will also be questioned and put to test. These results will also mean that future nanotechnology drugs will need to undergo several clinical trials first on non-human subjects and then on human subjects in order to ensure that they have no adverse effects have minimal on the brain or how their adverse effects on the brain can be counteracted at an early stage or reversed. This will pose a great challenge to nanotechnology drugs as their efficacy and safety will need to be assured through carrying out more studies.
Nanotechnology is a field with potential abilities that have not been exploited. Its application in pharmacy and medicine is as wide as in the diagnosis, medical equipment, drug manufacturing, and disease management. More studies should be carried out so that the application and use of nanotechnology in the medical field should be fully maximized. Their safety must be guaranteed through clinical trials that will give the assurance of safety in human beings.
- Thomas A. Faunce. Nanotherapeutics: new challenges for safety and cost-effectiveness regulation in Australia MJA Vol186 (4): 2007
- Borm, P. J., and Kreyling, W. Toxicological hazards of inhaled nanoparticles – potential implications for drug delivery. Journal of Nanosci Nanotechnol. 4:521- 31. 2004.
- Kreuter, J., Alvautdin, R. N., et al. Passage of peptides through the blood brain barrier with colloidal polymer particles (nanoparticles). Brain Res. 674(1): 171-4. 1995.
- Jiangxue, W., and Chunying C. Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicology Letters 183(1-3) 71-80. 2008.
- De Jong, W. H., and Borm, P. J. Drug delivery and nanoparticles: applications and hazards. International Journal of Nanomedicine. 3(2): 133-140. 2008.
- Heidi, Belden. What do the applications of nanotechnology mean to pharmacists? 2008.