Gold Nanoparticle: Synthesis, Characterization, Clinico-Pathological, Pathological, and Bio-Distribution Studies in Rabbits
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 33092
Gold Nanoparticle: Synthesis, Characterization, Clinico-Pathological, Pathological, and Bio-Distribution Studies in Rabbits

Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

Abstract:

This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 μg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters, and histopathological examination of various rabbits’ organs. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions were observed in liver, lungs and kidneys accompanied with mild absolute neutrophilia and significant monocytosis. The highest gold levels were found in the spleen and liver followed by lungs, and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: Gold nanoparticles, toxicity, pathology, hematology, liver function, kidney function.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1110455

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1844

References:


[1] Timbrell, J. A. (1998): Biomarkers in toxicology. Toxicology, 129, 1– 12.
[2] Schmid O., Möller W., Semmler-Behnke M., Ferron G. A., Karg E., Lipka J., Schulz H., Kreyling W. G., Stoeger T. Dosimetry and toxicology of inhaled ultrafine particles. Biomarkers. 2009 Jul;14 Suppl 1:67-73. doi: 10.1080/13547500902965617.
[3] Ghosh, P.; Han, G.; De, M.; Kim, C. K.; Rotello, V. M. (2008): Gold nanoparticles in delivery applications. Adv. Drug. Delivery Rev., 60, 1307–1315.
[4] Bhattacharya, R.; Mukherjee, P. (2008): Biological properties of naked metal nanoparticles. Adv. Drug. Delivery Rev.,60, 1289–1306.
[5] Connor, E. E.; Mwamuka, J.; Gole, A.; Murphy, C. J.; Wyatt, M. D. (2005): Gold nanoparticles are taken up by human cells but donot cause acute cytotoxicity. Small, 1, 325–327.
[6] Dobrovolskaia, S. E.; McNeil, M. A.(2007): Immunological properties of engineered nanoparticles. Nat. Nanotechnol., 2, 469–478.
[7] Patra, H. K.; Banerjee, S.; Chaudhuri, U.; Lahiri, P.; Dasgupta,A. K. (2007): Cell selective response to gold nanoparticles. Nanomedicine, 2007, 3, 111––119.
[8] Peng, G.; Tisch, U.; Adams, O.; Hakim, M.; Shehada, N.; Broza, Y. Y.; Billan, S.; Abdah-Bortnyad, R.; Kuten, R.; Haick, H. (2009): Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat. Nanotechnol., 4, 669–673.
[9] Pan, Y.; Neuss, S.; Leifert, A.; Fischler, M.; Wen, S.; Simon, U.; Schmid, G.; Brandau, W.; Jahnen-Dechent, W.(2007): Size-dependent cytotoxicity of gold nanoparticles. Small, 3, 1941–1949.
[10] Zhang, X. D.; Guo, M. L.; Wu, H. Y.; Sun, Y. M.; Ding, Y. Q.; Feng, X.; Zhang, L. A. (2009): Irradiation stability and cytotoxicity of gold nanoparticles for radiotherapy. Int. J. Nanomedicine, 4, 165–173.
[11] Sung, J. H.; Ji, J. H.; Park, J. D.; Song, M. Y.; Song, K. S.; Ryu, H. R.; Yoon, J. U.; Jeon, K. S.; Jeong, J.; Han, B. S.; Chung, Y. H.; Chang, H.K.; Lee, J. H.; Kim, D. W.; Kelman, B. J. and Yu, I. J. (2011): Subchronic inhalation toxicity of gold nanoparticles. J. Part. Fibre Toxicol., 2011, 8, 16–pp18.
[12] Turkevitch, J.; Stevenson, P.C.; Hillier, J. (1951): A study of the nucleation and growth process in the synthesis of colloidal gold. Faraday Soc. 1951, 11, 55–75.
[13] Alcantar, N.A.; Aydil, E.S.; Israelachvili, J.N. (2000): Polyethylene glycol-coated biocompatible surfaces. J. Biomed. Mater. Res., 5, 51(3):343-51.
[14] Liu, J. and Lu, Y. (2006) Preparation of aptamer-linked gold nanoparticle purple aggregates for colorimetric sensing of analytes. Nature Protocols;.1(1), 246-52.
[15] Alkilany, M. A.; Murphy, J. M. (2010): Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? Journal of nanoparticle research 12 (7), 2313-2333.
[16] Feldman, B. V.; Zinkl, J. G. and Jian, N. C. (2000): Schalm’s Veterinary Hematology. 5th ed., Lea and Fibiger, Philadelphia, USA.
[17] Weichselbaum, T. E. (1946): An accurate rapid method for determination of protein in small amounts of blood, serum and plasma. Am. J. Clin. Pathol., 7:40.
[18] Dumas, B. T. and Biggs, H. G. (1972): Standard Methods of Clinical Chemistry. Vol., 7: Academic Press, New York, USA, pp 175.
[19] Searcy, R. L.; Reardon, J. E. and Foreman, J. A. (1967): Estimation of urea. Am. J. Med. Tech., 33:15-20.
[20] Larsen K. Creatinine assay in the presence of protein with LKB 8600 Reaction Rate Analyser. Clin Chim Acta. 1972; 38: 475–476. doi: 10.1016/0009-8981(72)90146-5.
[21] Reitman A. and Frankel S., A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Amer. J. Clin. Path., 1957,28: 56-68.
[22] Terri, L. D. and Karen W. M. (1976): A spectrophotometric method for determination of glucose in blood serum. A freshman laboratory experiment for medically and biologically oriented students. J. Chem. Educ. 53 (2),126
[23] Kehoe, D. F.; Sullivan, D. M. and Smith, R. L. (1988): Determination of gold in animal tissue by graphite furnace atomic absorption spectrophotometry. J. Assoc. Off. Anal. Chem., 71(6):1153-1155
[24] Bancroft, J. D. and Gamble, M. (2008) Theory and Practice of Histological Techniques. 6th Edition, Churchill Livingstone, Elsevier, China.
[25] Snedecor, G. W. and Cochran, W. G. Statistical methods.(1980)7th Ed. Allid pacific, Bombay.
[26] Rai, V. R. and Bai, J. A. (2011): Nanoparticles and their Potential Application as Antimicrobials. In: Science against Microbial Pathogens: Communicating Current Research and Technological Advances, Mendez-Vilas, A. (Ed.). University of Mysore, India, pp: 197-209.
[27] Chah, S.; Hammond, M.; Zare, R. (2005): Gold nanoparticles as colorimetric sensor for protein conformational changes. Chem. Biol., 12(3): 3 23-8.
[28] Wang, Z.; Zdrojek, M., Melin, T. and Devel, M. (2008): Electric charge enhancements in carbon nanotubes: Theory and experiments. Phys. Rev. ; B 78, 085425 (2008).
[29] Zhang, X. D.; Wu, H. Y.; Wu, D.; Wang, Y. Y.; Chang, J. H.; Zhai, Z. B.; Meng, A. M.; Liu, P. X.; Zhang, L. A. and Fan, F. Y. (2010): Toxicologic effects of gold nanoparticles in-vivo by different administration routes. Int. J. Nanomed., 5:771-781.
[30] Das, S.; Debnath, N.; Mitra, S.; Datta, A. and Goswami, A. (2012): Comparative analysis of stability and toxicity profile of three differently capped gold nanoparticles for biomedical usage. Biometals, 25(5):1009- 1022.
[31] Sengupta, J.; Datta, P.; Patra, H. K.; Dasgupta, A. K. and Gomes, A. (2013): In-vivo interaction of gold nanoparticles after acute and chronic exposures in experimental animal models. J. Nanosci. Nanotechnol., 13(3):1660-1670.
[32] Dwivedi, P. D.; Misra, A.; Shanker, R. and Das, M. (2009): Are nanomaterials a threat to the immune system? Nanotoxicol., 3(1):19–26.
[33] Weiss, D. J.; Wardrop, K.; Jane and Schalm, O. W. (2010): Schalm’s Veterinary Hematology. 6th ed.; Wiley-Blackwell, USA.
[34] Hainfeld, J. F.; Slatkin, D. N. and Smilowitz, H. M. (2004): The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol., 49(18):309-315.
[35] Fent, G. M.; Casteel, S. W.; Kim, D. Y.; Kannan, R.; Katti, K.; Chanda, N. and Katti, K. (2009): Biodistribution of maltose and gum arabic hybrid gold nanoparticles after intravenous injection in juvenile swine. Nanomed. ; 5(2):128-135.
[36] Huang, X. L.; Zhang, B.; Ren, L.; Ye, S. F.; Sun, L. P.; Zhang, Q. Q.; Tan, M. C. and Chow, G. M. (2008): In-vivo toxic studies and biodistribution of near infrared sensitive Au-Au(2)S nanoparticles as potential drug delivery carriers. J. Mater. Sci.: Materials in Medicine, 19(7):2581-2588.
[37] Sonavane, G.; Tomoda, K. and Makino, K. (2008): Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf. B, Biointerfaces, 66(2):274-280.
[38] Lipka, J.; Semmler-Behnke, M.; Sperling, R.A.; Wenk, A.; Takenaka, S.; Schleh, C.; Kissel, T.; Parak, W. J. and Kreyling, W. G. (2010): Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials, 31(25):6574-6581.
[39] Cho, W. S.; Cho, M.; Jeong, J.; Choi, M.; Cho, H. Y.; Han, B. S.; Kim, S.H.; Kim, H.O.; Lim, Y.T.; Chung, B.H. and Jeong, J. (2009 a): Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. Toxicol. Appl. Pharmacol., 236(1):16-24.
[40] Doudi, M. and Setorki, M. (2014): The acute liver injury in rat caused by of gold nanoparticles. Nano medicine J. V. (1), I (4), P. 248.
[41] Cho, W. S.; Kim, S.; Han, B. S.; Son, W. C. and Jeong, J. (2009 b): Comparison of gene expression profiles in mice liver following intravenous injection of 4 and 100 nm-sized PEG-coated gold nanoparticles. Toxicol. Lett. , 191(1):96-102.
[42] Terentyuk, G. S.; Maslyakova, G. N.; Suleymanova, L. V.; Khlebtsov, B. N.; Kogan, B. Y.; Akchurin, G. G.; Shantrocha, A. V.; Maksimova, I. L.; Khlebtsov, N. G. and Tuchin, V. V. (2009): Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery. J. Biophotonics, 2(5):292- 302.
[43] Abdelhalim, M. A. and Jarrar, B. M. (2011 b): Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles. Lipids Health Dis., 10:163.
[44] Chen, Y. S.; Hung, Y. C.; Liau, I. and Huang, G.S. (2009): Assessment of the In-vivo Toxicity of gold nanoparticles. Nanoscale Res. Lett., 4(8):858-864.
[45] Lasagna-Reeves, C.; Gonzalez-Romero, D.; Barria, M. A.; Olmedo, I.; Clos, A.; Sadagopa, Ramanujam. V.M.; Urayama, A.; Vergara, L.; Kogan, M.J. and Soto, C. (2010): Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem. Biophys. Res. Commun., 393(4):649-655.