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:

http://youtu.be/2VcNpl8-PRI

• 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).

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•                 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 modification 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.