Pharmacokinetic Aspects of Carbon Nanotubes: Improving Outcomes of Functionalization

Author(s): Elaheh Entezar-Almahdi , Mohammad Hossein Morowvat* .

Journal Name: Current Nanoscience

Volume 15 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Carbon nanotubes (CNTs) are allotropes of carbon with a cylindrical nanostructure. Thanks to their electrical, mechanical and optical properties, they have been widely used for different pharmaceutical, biological and biomedical applications. To understand the biofate of the CNTs in the body, their pharmacokinetic properties should be revealed appropriately.

Objective: To review the available literature, regarding the different pharmacokinetic properties including absorption, distribution, metabolism and elimination of the functionalized CNTs.

Results: Surface coating or functionalizing the CNTs has huge effects on their pharmacokinetics, ADME properties and also their biodistribution profile. During the metabolism, CNTs could be destroyed directly or their surface functional groups might be removed. Both biliary and renal pathways are known for CNTs elimination.

Conclusion: Additional optimization on the CNTs formulation is required to enhance their absorption and bioavailability. Besides, regarding the increased scientific attention towards the CNTs toxicity, it could be suggested that determining the bioavailability of CNTs is a critical parameter to determine the CNTs safety.

Keywords: ADME, biodistribution, carbon nanotube, functionalization, nanomaterials, nanoscience, PEGylation, pharmacokinetics.

[1]
Boczkowski, J.; Lanone, S. Potential uses of carbon nanotubes in the medical field: How worried should patients be? Nanomedicine , 2007, 2(4), 407-410.
[2]
Beg, S.; Rizwan, M.; Sheikh, A.M.; Hasnain, M.S.; Anwer, K.; Kohli, K. Advancement in carbon nanotubes: Basics, biomedical applications and toxicity. J. Pharm. Pharmacol., 2011, 63(2), 141-163.
[3]
De Volder, M.F.; Tawfick, S.H.; Baughman, R.H.; Hart, A.J. Carbon nanotubes: Present and future commercial applications. Science, 2013, 339(6119), 535-539.
[4]
Iijima, S. Helical microtubules of graphitic carbon. Nature, 1991, 354(6348), 56-58.
[5]
Amenta, V.; Aschberger, K. Carbon nanotubes: Potential medical applications and safety concerns. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2015, 7(3), 371-386.
[6]
Yang, S.T.; Fernando, K.; Liu, J.H.; Wang, J.; Sun, H.F.; Liu, Y.; Chen, M.; Huang, Y.; Wang, X.; Wang, H. Covalently PEGylated carbon nanotubes with stealth character in vivo. Small, 2008, 4(7), 940-944.
[7]
Liu, Z.; Tabakman, S.; Welsher, K.; Dai, H. Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery. Nano Res., 2009, 2(2), 85-120.
[8]
Jones, D.J.; Swarbrick, J.; Boylan, J. Encyclopedia of Pharmaceutical Technology, 2nd ed; Taylor & Francis: New York, 2002.
[9]
United States Food and Drug Administration, Center for Drug Evaluation and Research. Available from: http://www.fda.gov/cd-er/regulatory/default.htm (Accessed on: March 25, 2018) .
[10]
National Archives and Records Administration, Code of Federal Regulations, Title 21, Food and Drugs, Food and Drug Administration, Department of Health and Human Services, Part 320, Bioavailability and Bioequivalence Requirements.
[11]
Benet, L.Z.; Galeazzi, R.L. Noncompartmental determination of the steady‐state volume of distribution. J. Pharm. Sci., 1979, 68(8), 1071-1074.
[12]
Rowland, M.; Benet, L.Z.; Graham, G.G. Clearance concepts in pharmacokinetics. J. Pharmacokinet. Biopharm., 1973, 1(2), 123-136.
[13]
Craig, C.R.; Stitzel, R.E. Modern Pharmacology with Clinical Applications, 6th ed; Lippincott Williams & Wilkins: Philadelphia, 2004.
[14]
Fröhlich, E.; Roblegg, E. Models for oral uptake of nanoparticles in consumer products. Toxicology, 2012, 291(1), 10-17.
[15]
Bergin, I.L.; Witzmann, F.A. Nanoparticle toxicity by the gastrointestinal route: Evidence and knowledge gaps. Int. J. Biomed. Nanosci. Nanotechnol., 2013, 3(1-2), 163-210.
[16]
Deng, X.; Jia, G.; Wang, H.; Sun, H.; Wang, X.; Yang, S.; Wang, T.; Liu, Y. Translocation and fate of multi-walled carbon nanotubes in vivo. Carbon, 2007, 45(7), 1419-1424.
[17]
Ito, Y.; Venkatesan, N.; Hirako, N.; Sugioka, N.; Takada, K. Effect of fiber length of carbon nanotubes on the absorption of erythropoietin from rat small intestine. Int. J. Pharm., 2007, 337(1), 357-360.
[18]
Philbrook, N.A.; Walker, V.K.; Afrooz, A.N.; Saleh, N.B.; Winn, L.M. Investigating the effects of functionalized carbon nanotubes on reproduction and development in Drosophila melanogaster and CD-1 mice. Reprod. Toxicol., 2011, 32(4), 442-448.
[19]
Coyuco, J.C.; Liu, Y.; Tan, B-J.; Chiu, G. Functionalized carbon nanomaterials: Exploring the interactions with Caco-2 cells for potential oral drug delivery. Int. J. Nanomedicine, 2011, 6, 2253-2263.
[20]
Wang, H.; Yang, S-T.; Cao, A.; Liu, Y. Quantification of carbon nanomaterials in vivo. Acc. Chem. Res., 2012, 46(3), 750-760.
[21]
Jacobsen, N.R.; Møller, P.; Clausen, P.A.; Saber, A.T.; Micheletti, C.; Jensen, K.A.; Wallin, H.; Vogel, U. Biodistribution of carbon nanotubes in animal models. Basic Clin. Pharmacol. Toxicol., 2017, 121, 30-43.
[22]
Brigger, I.; Dubernet, C.; Couvreur, P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev., 2012, 64, 24-36.
[23]
Singh, R.; Pantarotto, D.; Lacerda, L.; Pastorin, G.; Klumpp, C.; Prato, M.; Bianco, A.; Kostarelos, K. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc. Natl. Acad. Sci. USA, 2006, 103(9), 3357-3362.
[24]
Liu, Z.; Cai, W.; He, L.; Nakayama, N.; Chen, K.; Sun, X.; Chen, X.; Dai, H. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat. Nanotechnol., 2007, 2(1), 47-52.
[25]
Ali-Boucetta, H.; Kostarelos, K. Pharmacology of carbon nanotubes: Toxicokinetics, excretion and tissue accumulation. Adv. Drug Deliv. Rev., 2013, 65(15), 2111-2119.
[26]
Liu, Z.; Sun, X.; Nakayama-Ratchford, N.; Dai, H. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano, 2007, 1(1), 50-56.
[27]
Bhirde, A.A.; Patel, S.; Sousa, A.A.; Patel, V.; Molinolo, A.A.; Ji, Y.; Leapman, R.D.; Gutkind, J.S.; Rusling, J.F. Distribution and clearance of PEG-single-walled carbon nanotube cancer drug delivery vehicles in mice. Nanomedicine , 2010, 5(10), 1535-1546.
[28]
Zhao, X.; Tian, K.; Zhou, T.; Jia, X.; Li, J.; Liu, P. PEGylated multi-walled carbon nanotubes as versatile vector for tumor-specific intracellular triggered release with enhanced anti-cancer efficiency: Optimization of length and PEGylation degree. Colloids Surf. B Biointerfaces, 2018, 168, 43-49.
[29]
McCabe, N.; De, S.; Vasanji, A.; Brainard, J.; Byzova, T. Prostate cancer specific integrin αvβ3 modulates bone metastatic growth and tissue remodeling. Oncogene, 2007, 26(42), 6238-6243.
[30]
Hosotani, R.; Kawaguchi, M.; Masui, T.; Koshiba, T.; Ida, J.; Fujimoto, K.; Wada, M.; Doi, R.; Imamura, M. Expression of integrin αvβ3 in pancreatic carcinoma: Relation to MMP-2 activation and lymph node metastasis. Pancreas, 2002, 25(2), e30-e35.
[31]
Gasparini, G.; Brooks, P.C.; Biganzoli, E.; Vermeulen, P.B.; Bonoldi, E.; Dirix, L.Y.; Ranieri, G.; Miceli, R.; Cheresh, D.A. Vascular integrin alpha (v) beta3: A new prognostic indicator in breast cancer. Clin. Cancer Res., 1998, 4(11), 2625-2634.
[32]
Li, Z.; de Barros, A.L.B.; Soares, D.C.F.; Moss, S.N.; Alisaraie, L. Functionalized single-walled carbon nanotubes: Cellular uptake, biodistribution and applications in drug delivery. Int. J. Pharm., 2017, 524(1-2), 41-54.
[33]
Desgrosellier, J.S.; Cheresh, D.A. Integrins in cancer: Biological implications and therapeutic opportunities. Nat. Rev. Cancer, 2010, 10(1), 9-22.
[34]
Wang, H.; Wang, J.; Deng, X.; Sun, H.; Shi, Z.; Gu, Z.; Liu, Y.; Zhaoc, Y. Biodistribution of carbon single-wall carbon nanotubes in mice. J. Nanosci. Nanotechnol., 2004, 4(8), 1019-1024.
[35]
Zhao, L.; Wen, S.; Zhu, M.; Li, D.; Xing, Y.; Shen, M.; Shi, X.; Zhao, J. 99mTc-labelled multifunctional polyethylenimine-entrapped gold nanoparticles for dual mode SPECT and CT imaging. Artif. Cells Nanomed. Biotechnol., 2018, 46, 488-498.
[36]
Lacerda, L.; Soundararajan, A.; Singh, R.; Pastorin, G.; Al-Jamal, K.T.; Turton, J.; Frederik, P.; Herrero, M.A.; Li, S.; Bao, A. Dynamic imaging of functionalized multi‐walled carbon nanotube systemic circulation and urinary excretion. Adv. Mater., 2008, 20(2), 225-230.
[37]
McDevitt, M.R.; Chattopadhyay, D.; Jaggi, J.S.; Finn, R.D.; Zanzonico, P.B.; Villa, C.; Rey, D.; Mendenhall, J.; Batt, C.A.; Njardarson, J.T. PET imaging of soluble yttrium-86-labeled carbon nanotubes in mice. PLoS One, 2007, 2(9)e907
[38]
Huang, H.; Lovell, J.F. Advanced functional nanomaterials for theranostics. Adv. Funct. Mater., 2017, 27(2)1603524
[39]
Hong, S.Y.; Tobias, G.; Al-Jamal, K.T.; Ballesteros, B.; Ali-Boucetta, H.; Lozano-Perez, S.; Nellist, P.D.; Sim, R.B.; Finucane, C.; Mather, S.J. Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging. Nat. Mater., 2010, 9(6), 485-490.
[40]
Martin, R.; Falicov, L. Resonant Raman scattering. Light scattering in Solids I: Springer; Switzerland AG, 1983, pp. 79-145.
[41]
Zavaleta, C.; De La Zerda, A.; Liu, Z.; Keren, S.; Cheng, Z.; Schipper, M.; Chen, X.; Dai, H.; Gambhir, S. Noninvasive Raman spectroscopy in living mice for evaluation of tumor targeting with carbon nanotubes. Nano Lett., 2008, 8(9), 2800-2805.
[42]
Smith, B.R.; Zavaleta, C.; Rosenberg, J.; Tong, R.; Ramunas, J.; Liu, Z.; Dai, H.; Gambhir, S.S. High-resolution, serial intravital microscopic imaging of nanoparticle delivery and targeting in a small animal tumor model. Nano Today, 2013, 8(2), 126-137.
[43]
Welsher, K.; Sherlock, S.P.; Dai, H. Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window. Proc. Natl. Acad. Sci. USA, 2011, 108(22), 8943-8948.
[44]
Heller, D.A.; Baik, S.; Eurell, T.E.; Strano, M.S. Single‐walled carbon nanotube spectroscopy in live cells: Towards long‐term labels and optical sensors. Adv. Mater., 2005, 17(23), 2793-2799.
[45]
Hong, G.; Lee, J.C.; Robinson, J.T.; Raaz, U.; Xie, L.; Huang, N.F.; Cooke, J.P.; Dai, H. Multifunctional in vivo vascular imaging using near-infrared II fluorescence. Nat. Med., 2012, 18(12), 1841-1846.
[46]
Welsher, K.; Liu, Z.; Sherlock, S.P.; Robinson, J.T.; Chen, Z.; Daranciang, D.; Dai, H. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nat. Nanotechnol., 2009, 4(11), 773-780.
[47]
Yang, K.; Hu, L.; Ma, X.; Ye, S.; Cheng, L.; Shi, X.; Li, C.; Li, Y.; Liu, Z. Multimodal imaging guided photothermal therapy using functionalized graphene nanosheets anchored with magnetic nanoparticles. Adv. Mater., 2012, 24(14), 1868-1872.
[48]
Avti, P.K.; Hu, S.; Favazza, C.; Mikos, A.G.; Jansen, J.A.; Shroyer, K.R.; Wang, L.V.; Sitharaman, B. Detection, mapping, and quantification of single walled carbon nanotubes in histological specimens with photoacoustic microscopy. PLoS One, 2012, 7(4)e35064
[49]
Gong, H.; Peng, R.; Liu, Z. Carbon nanotubes for biomedical imaging: The recent advances. Adv. Drug Deliv. Rev., 2013, 65(15), 1951-1963.
[50]
Wang, C.; Ma, X.; Ye, S.; Cheng, L.; Yang, K.; Guo, L.; Li, C.; Li, Y.; Liu, Z. Protamine functionalized single-walled carbon nanotubes for stem cell labeling and in vivo Raman/magnetic resonance/photoacoustic triple‐modal imaging. Adv. Funct. Mater., 2012, 22(11), 2363-2375.
[51]
Mahajan, S.; Patharkar, A.; Kuche, K.; Maheshwari, R.; Deb, P.K.; Kalia, K.; Tekade, R.K. Functionalized carbon nanotubes as emerging delivery system for the treatment of cancer. Int. J. Pharm., 2018, 548(1), 540-558.
[52]
Al Faraj, A.; Fauvelle, F.; Luciani, N.; Lacroix, G.; Levy, M.; Cremillieux, Y.; Canet-Soulas, E. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques. Int. J. Nanomedicine, 2011, 6, 351-361.
[53]
Doan, B.T.; Seguin, J.; Breton, M.; Beherec, R.L.; Bessodes, M.; Rodríguez-Manzo, J.A.; Banhart, F.; Beloeil, J.C.; Scherman, D.; Richard, C. Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging. Contrast Media Mol. Imaging, 2012, 7(2), 153-159.
[54]
Yang, S-T.; Wang, X.; Jia, G.; Gu, Y.; Wang, T.; Nie, H.; Ge, C.; Wang, H.; Liu, Y. Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol. Lett., 2008, 181(3), 182-189.
[55]
Allen, B.L.; Kichambare, P.D.; Gou, P.; Vlasova, I.I.; Kapralov, A.A.; Konduru, N.; Kagan, V.E.; Star, A. Biodegradation of single-walled carbon nanotubes through enzymatic catalysis. Nano Lett., 2008, 8(11), 3899-3903.
[56]
Kagan, V.E.; Konduru, N.V.; Feng, W.; Allen, B.L.; Conroy, J.; Volkov, Y.; Vlasova, I.I.; Belikova, N.A.; Yanamala, N.; Kapralov, A. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nat. Nanotechnol., 2010, 5(5), 354-359.
[57]
Yang, S-T.; Wang, H.; Meziani, M.J.; Liu, Y.; Wang, X.; Sun, Y-P. Biodefunctionalization of functionalized single-walled carbon nanotubes in mice. Biomacromolecules, 2009, 10(7), 2009-2012.
[58]
Yang, S-T.; Luo, J.; Zhou, Q.; Wang, H. Pharmacokinetics, metabolism and toxicity of carbon nanotubes for biomedical purposes. Theranostics, 2012, 2(3), 271-282.
[59]
Cherukuri, P.; Gannon, C.J.; Leeuw, T.K.; Schmidt, H.K.; Smalley, R.E.; Curley, S.A.; Weisman, R.B. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc. Natl. Acad. Sci. USA, 2006, 103(50), 18882-18886.
[60]
Cedervall, T.; Lynch, I.; Lindman, S.; Berggård, T.; Thulin, E.; Nilsson, H.; Dawson, K.A.; Linse, S. Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl. Acad. Sci. USA, 2007, 104(7), 2050-2055.
[61]
Liu, Z.; Davis, C.; Cai, W.; He, L.; Chen, X.; Dai, H. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by raman spectroscopy. Proc. Natl. Acad. Sci. USA, 2008, 105(5), 1410-1415.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 5
Year: 2019
Page: [454 - 459]
Pages: 6
DOI: 10.2174/1573413715666181204113525
Price: $58

Article Metrics

PDF: 28
HTML: 1