This blog provides a summary of information about the application of gold nanoparticles technology in developing new drug delivery systems. Drug Delivery is an important area of study in nanomedicine.To begin, here's a short overeview of nanomedicine:
- Overview of gold nanoparticles in drug delivery
One of the
most active research areas of nanomedicine is drug delivery using different
types of nanoparticles. Nanoparticles are defined as the smallest unit of
matter that contains the same properties and can be transported. There are diverse types of
nanoparticles that have been synthesized and evaluated. Nanomaterial-based
agents tested as carriers in drug delivery systems include liposomes, polymers,
dendrimers, silicon or carbon materials, and magnetic nanoparticles. The
purpose of using these nanocarriers is to eliminate some of the limitations of
previously used drug delivery systems such as poor bioavailability and
intestinal absorption, to reduce toxicity and
side effects, and to increase therapeutic effectiveness by targeting a
specific cell (Yah C., 2013).
Colloidal gold, also known as gold nanoparticles, is a
suspension (or colloid) of nanometer-sized particles of gold. This nanoparticle
exhibit significantly novel and distinct chemical, physical, and biological
properties, and functionality due to its nanoscale (10-9m) size ( Mody V. V., 2010). The biological
study of gold nanoparticles (GNP) occurred only
in 1971, when the British researchers Faulk and Taylor described a method of
antibody conjugation with colloidal gold for direct electron microscopy visualization
of the surface antigens of salmonellae. The study was later continued by
conjugating colloidal gold with immunoglobulins and other molecules – in
different spheres of biology and medicine. Over the past 40 years, there have
been many studies devoted to the application of functionalized nanoparticles –
conjugates with different biomacromolecules (antibodies, lectins, enzymes,
aptamers, etc.) (Jain S., 2010). These conjugates can be synthesized using different
methods including chemical, physical, and green methods (Arvizo R., 2010). Figure 1. shows some of these methods.
Figure 1. (Arvizo R., 2010)
- Benefits the technology
o Gold nanoparticles can be used
in targeted drug delivery. Targeted drug delivery is the primary goal of
developing drugs in cancer therapy. It is meant to minimize the side effects of
drugs by targeting the infected tissue and delivering drugs sufficiently
without harming other cells (Khan A., 2014). GNPs are used because:
§ Due
to small size, shape and other physical and chemical properties, they can
easily reach to the targeted site with blood flow and enter the cell.
§ Gold
nanoparticles have high surface area which provide dense drug loading.
§ These
particles are biocompatible and are can easily be conjugated with small
biomolecules such as proteins, enzymes, carboxylic acid, DNA, and amino acids (Ochekpe N., 2009).
o Gold nanoparticles can be used
to improve drug delivery systems such as chemotherapy and help to develop new
drug in long term, which can lead to improvements in cancer treatment, genetic
diseases and other medical achievements (Khan A., 2014).
- Limitations and guidelines for the future
Due to some current limitations using nanoparticles as drug delivery system is still in its early stage and requires more research. One of the challenges is producing these nano drugs in large-scale. Delivering these drugs require laboratory space and expert knowledge. Therefore, employing material and professionals for producing these drugs may be expensive. Also, the efforts in the past decade were made on smaller scales. (Bamrungsap, S., n.d.). In addition, our information about the interaction mechanisms between nanoparticles and our cell's outer defences – the cell membrane– does not include great details. Without this it is impossible to determine how dangerous they are and whether their ability to penetrate and destroy cells can ever be harnessed for good ends, such as in the fight against cancer (Neutrons Reveal Potential Dangers of Gold Nanoparticles—Pharma's Drug Delivery Agent of the Future, 2013).
- Health and safety precautions
o
There are some potential health
concerns regarding toxicity of AuNPs. Overall, Toxicity of AuNPs is generally
accepted to be dependent on particle size, shape, and surface charge and
chemistry. However, it is thought that in very small sizes, these particles can
easily pass through healthy cells and be transported within the body. This may
affects some organs such as liver and spleen in long term (Silva J., 2014).
o
Some studies have shown that
very small particles (1.4 and 5 nm in diameter) seem to be capable to enter the
nucleus, where they can interact with DNA and cause molecular disturbance (Silva
J., 2014).
o
Another study has revealed that
charged GNPs have a higher toxicity than uncharged GNPs and cations are more
toxic than anions (Silva J., 2014).
o
However, since this effect is
seen in a very long term and the side effect less significant than other drug
delivery systems, GNPs are considered to be safe to use. Besides, by further
experiments, scientists seek for a coating to these particles (Akhter, S, 2012).
- Current status of the research
o Recent
achievements in this area include studies about the characteristics of gold
nanoparticles and using GNPs in technology and imaging cancer cells. Drugs have
not yet been used to treat patients.
o A
research team from the University of Missouri performed an experiment on dogs it was
hypothesised that these particles, injected intravenously, would indicate
tumours but not healthy brain tissue. This is because of punctured blood
vessels that are connected to a brain tumour which would allow the particles to
bleed out of these vessels and target the tumour. In this treatment radioactive
gold nanoparticles directly to a prostate tumour, causing it to shrink. This
treatment was also performed on mice and in both experiments there were no side
effects seen. Also, further lab–based treatments were done on pancreatic cancer
cells and breast cancer cells using gold nanoparticles (Clark, L., 2012).
- Environmental risks associated with use of technology
o The
environmental challenge of using metallic nanoparticles such as gold is related
to their synthesis methods. For example, synthetic techniques based on the
reduction of metal ions with sodium citrate or sodium borohydride, followed by
surface modiļ¬cation of the produced particles with suitable capping ligands and
organic solvents, raised environmental concerns, because of the toxic compounds
used in the process. One of the suggested methods to solve this issue is using
a green chemical approach for the synthesis of gold nanoparticles. In this
approach biosynthetic methods are used. This refers to using organic molecules
such as folic acid or microorganisms including bacteria and fungi (Marsili, E., 2010).
- Conclusion
Over the past
decade Colloidal gold has gained a lot of attention in the
nanomedicine area and many researches and studies have led to development of
chemical and technological conjugates of GNPs. Moreover, although the
development of drug delivery systems is just emerging, it shows a promising
future. Gold nanoparticles can allow
increasingly specific and accelerated drug delivery, which minimizes unintended
side effects, increases tolerable dosages. Nonetheless, long-term studies in
higher organisms are necessary to further characterise the safety of GNPs as
therapeutic agents, so they can be safely administrated to humans without
concerns about late toxicity symptoms (Arvizo, R., 2010). Therefore, my
opinion is that using gold nanoparticles in drug delivery should not yet be regulated
and further experiments and studies should be done to create standards for
testing and using gold nanoparticles in a larger scale.
References:
Akhter, S., Ahmad, M., Ahmad, F., Storm, G.,
& Kok, R. (2012). Gold nanoparticles in theranostic oncology: Current
state-of-the-art. Expert Opinion on Drug Delivery, 9(10),
1225-1243.
Arvizo, R., Bhattacharya, R., & Mukherjee, P.
(2010). Gold nanoparticles: Opportunities and Challenges in Nanomedicine. Expert
Opinion on Drug Delivery, 7(6), 753–763. doi:10.1517/17425241003777010
Bamrungsap, S., Zhao, Z., Chen, T., Wang, L.,
Li, C., Fu, T., & Tan, W. (n.d.). Nanotechnology in Therapeutics. Retrieved
March 4, 2015, from
http://www.medscape.com/viewarticle/770397_5
Clark, L. (2012, October 16). Gold nanoparticle
cancer treatment in dogs has no observed side effects (Wired UK). Retrieved
March 4, 2015, from
http://www.wired.co.uk/news/archive/2012-10/16/gold-nanoparticles-cancer-dogs
Dykman,
L. A., & Khlebtsov, N. G. (2011). Gold Nanoparticles in Biology and
Medicine: Recent Advances and Prospects . Acta Naturae, 3(2), 34–55.
Jain, S., Hirst, D. G., & O’Sullivan, J. M.
(2012). Gold nanoparticles as novel agents for cancer therapy. The British Journal of Radiology, 85(1010), 101–113.
doi:10.1259/bjr/59448833
Khan, A., Rashid, R., Murtaza, G., & Zahra,
A. (2014). Gold Nanoparticles: Synthesis and Applications in Drug Delivery. Tropical
Journal of Pharmaceutical Research, 13(7), 1169-1177.
Marsili, E., Das, S. (2010). A Green Chemical
Approach for the Synthesis of Gold nanoparticles: Characterization and
Mechanistic Aspect. Review in Environmental Science and Biotechnology, 9.
Retrieved March 3, 2015, from
http://www.academia.edu/223412/A_green_chemical_approach_for_the_synthesis_of_gold_nanoparticles_characterization_and_mechanistic_aspect
Mody, V. V., Siwale, R., Singh, A., & Mody,
H. R. (2010). Introduction to metallic nanoparticles. Journal of Pharmacy and Bioallied Sciences, 2(4), 282–289.
doi:10.4103/0975-7406.72127
Neutrons Reveal Potential Dangers of Gold
Nanoparticles—Pharma's Drug Delivery Agent of the Future. (2013, June 7).
Retrieved March 4, 2015, from
http://phys.org/news/2013-06-neutrons-reveal-potential-dangers-gold.html
Ochekpe, N., Olorunfemi, P., & Ngwuluka, N.
(2009). Nanotechnology and Drug Delivery Part 1: Background and Applications. Tropical
Journal of Pharmaceutical Research, 8(3), 265-274.
Silva J., Fernandes A. & Baptista P.,
(2014). Application of Nanotechnology in Drug Delivery, Application of
Nanotechnology in Drug Delivery, PhD. Ali Demir Sezer (Ed.), ISBN:
978-953-51-1628-8, InTech, DOI: 10.5772/58424. Retrieved March 4, 2015 from:
http://www.intechopen.com/books/application-of-nanotechnology-in-drug-delivery/application-of-nanotechnology-in-drug-delivery
Safari, J., & Zarnegar, Z. (2013). Advanced
drug delivery systems: Nanotechnology of health design A review.Journal of
Saudi Chemical Society, 18(2), 85-99. Retrieved March 4, 2015,
from http://www.sciencedirect.com/science/article/pii/S1319610312001986
Silverman, J. (2007, August 3). Gold
Nanoparticles. Retrieved March 4, 2015, from
http://health.howstuffworks.com/medicine/modern-technology/gold-nanotech.htm
Yah, C. (2013). The toxicity of Gold
Nanoparticles in relation to their physiochemical properties. Biomedical
Research, 24(3), 400-413.
