Toxicology Perspective of Nanopharmaceuticals: A Critical Review

DOI:

https://doi.org/10.37285/ijpsn.2011.4.1.1

Authors

  • S C Patel
  • Patel R.C
  • Saiyed M.A.

Abstract

For the last 10 years pharmaceutical research and industry has elucidated several innovations and practices in pharmaceutical nanotechnology. Due to the increasing use of nanoparticles, the risk of human exposure rapidly increases and reliable toxicity test systems are urgently needed. Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on the relationship between the physical and chemical properties of nanostructures with induction of toxic biological responses. It involves their unique biodistribution, clearance, accumulation, immune response and metabolism. An understanding of the relationship between the physical and chemical properties of the nanostructure and their in-vivo behavior would provide a basis for assessing toxic response and more importantly could lead to better predictive models for assessing toxicity. The current regulations for nanoparticles containing products are still in a nascent stage. The advantages of nanoparticles led to failures in noticing the toxic outcomes in living organisms. Major changes are required by considering several factors including environmental, health and safety issues. The rapid commercialization of nanotechnology requires thoughtful open discussion of broader societal impacts and urgent toxicological oversight action.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

Nanotoxicology, toxicity, pharmacokinetic, physicochemical properties, immune response

Downloads

Published

2011-05-31

How to Cite

1.
Patel SC, R.C P, M.A. S. Toxicology Perspective of Nanopharmaceuticals: A Critical Review. Scopus Indexed [Internet]. 2011 May 31 [cited 2024 Dec. 21];4(1):1287-95. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/405

Issue

Section

Review Articles

References

Agashe HB, Dutta T, Garg M, Jain NK. Investigations on the toxicological profile of functionalized fifth-generation poly(propylene imine) dendrimer. J. Pharm. Pharmacol. 58: 1491-1498 (2006).

Akerman ME, Chan WC, Laakkonen P, Bhatia SN, Ruoslahti E. Nanocrystal targeting in-vivo. Proc Natl Acad Sci. 99: 12617-12621 (2002).

Ballou B, Lagerholm BC, Ernst LA, Bruchez MP, Waggoner AS. Noninvasive imaging of quantum dots in mice. Bioconjug. Chem. 15: 79-86 (2004).

Borm P, Klaessig FC, Landry TD, Moudgil B, Pauluhn J, Thomas K, Trottier R, Wood S. Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles. Toxicol Sci. 90: 23-32 (2006).

Caruthers SD, Wickline SA, Lanza GM. Nanotechnological applications in medicine. Curr Opin Biotech. 18: 26-30 (2007).

Cavallaro G, Maniscalco L, Licciardi M, Giammona G. Tamoxifenloaded polymeric micelles: preparation, physico-chemical characterization and in-vitro evaluation studies. Macromol Biosci. 4: 1028-1038 (2004).

Champion JA, Smitragotri S. Role of target geometry in phagocytosis. Proc. Natl. Acad. Sci. U. S. A. 103: 4930-4934 (2008).

Chauhan AS, Jain NK, Diwan PV, Khopade AJ. Solubility enhancement of indomethacin with poly(amidoamine) dendrimers and targeting to inflammatory regions of arthritic rats. J Drug Target. 12: 575-583 (2004).

Chen HT, Neerman MF, Parrish AR, Simanek EE. Cytotoxicity, hemolysis, and acute in-vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. J. Am. Chem. Soc. 126: 10044–10048 (2004).

Cherukuri P, Gannon CJ, Leeuw TK, Schmidt HK, Smalley RE, Curley SA, Weisman RB. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc. Natl. Acad. Sci. U. S. A. 103: 18882–18886 (2006).

Curtis J, Greenberg M, Kester J, Phillips S, Krieger G. Nanotechnology and nanotoxicology: a primer for clinicians. Toxicol. Sci. 25: 245–260 (2006).

Dagar S, Krishnadas A, Rubinstein I, Blend MJ, Onyuksel H. VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in-vivo studies. J Control Release. 91: 123-133 (2003).

Davidson RN, Croft SL, Scott A, Maini M, Moody AH, Bryceson AD. Liposomal amphotericin B in drug-resistant visceral leishmaniasis. Lancet. 337: 1061- 1062 (1991).

De Jesus OLP, Ihre HR, Gagne L, Frechet JMJ, Szoka FC. Polyester dendritic systems for drug delivery applications: in-vitro and in-vivo evaluation. Bioconjug. Chem. 13: 453–461 (2002).

De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJAM, Geertsma RE. Particle size-dependent organ distribution of gold nanoparticles after intravenous injection. Biomaterials. 29: 1912-1919 (2008).

Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nat. Nanotechnol. 2: 469-478 (2007).

Elder A, Yang H, Gwiazda R, Teng X, Thurston S, He H, Oberdörster G. Testing nanomaterials of unknown toxicity: an example based on platinum nanoparticles of different shapes. Adv. Mater. 19: 3124–3129 (2004).

Fischer HC, Chan WCW. Nanotoxicity: the growing need for in-vivo study. Curr. Opin. Biotechnol. 18: 565–571 (2007).

Fischer HC, Liu L, Pang KS, Chan WCW. Pharmacokinetics of nanoscale quantum dots: in-vivo distribution, sequestration, and clearance in the rat. Adv. Funct. Mater. 16: 1299-1305 (2006).

Fraczek A, Menaszek E, Paluszkiewicz C, Blazewicz M. Comparative in-vivo biocompatability study of single and multi-wall carbon nanotubes. Acta Biomater. 4: 1593–1602 (2008).

Gandon Y, Heautot JF, Brunet F, Guyader D, Deugnier Y, Carsin M. Superparamagnetic iron oxide: clinical time-response study. Eur J Radiol. 12: 195-200 (1991).

Garnett MC, Kallinteri P. Nanomedicines and nanotoxicology: some physiological principles. Occup. Med. 56: 307–311 (2006).

Guaglianone P, Chan K, DelaFlor-Weiss E, Hanisch R, Jeffers D, Sharma D, et al. Phase I and pharmacologic study of liposomal daunorubicin (DaunoXome). Invest New Drugs. 12: 103-110 (1994).

Hall JB, Dobrovolskaia MA, Patri AK, McNeil SE. Characterization of nanoparticles for therapeutics. Nanomedicine. 2: 789-803 (2007).

Herzog E, Casey A, Lyng FM, Chambers G, Byrne HJ, Davoren M, A new approach to the toxicity testing of carbon-based nanomaterials-the clonogenic assay. Toxicol. Lett. 174: 49-60 (2007).

Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E, et al. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res.8: 1038-1044 (2002).

Italia JL, Bhatt DK, Bhardwaj V, Tikoo K, Kumar MN, PLGA nanoparticles for oral delivery of cyclosporine: nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral. J. Control. 119: 197–206 (2007).

Kagan VE, Bayir H, Shvedova AA. Nanomedicine and nanotoxicology: two sides of the same coin, Nanomedicine. 1: 313-316 (2005).

Kakizawa Y, Harada A, Kataoka K. Glutathione-sensitive stabilization of block copolymer micelles composed of antisense DNA and thiolated poly(ethylene glycol)-block-poly(L-lysine): a potential carrier for systemic delivery of antisense DNA. Biomacromolecules.2: 491-497 (2001).

Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, et al. Phase I and pharmacokinetic study of Genexol-PM, a cremophorfree, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 10: 3708-3716 (2004).

Kipen HM, Laskin DL. Smaller is not always better: nanotechnology yields nanotoxicology. Am. J. Physiol. Lung Cell. Mol. Physiol. 289: L696–L697 (2005).

Kobayashi H, Kawamoto S, Jo SK, Bryant Jr HL, Brechbiel MW, Star RA. Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores. Bioconjug Chem.14: 388-394 (2003).

Koo O, Rubinstein I, Onyuksel H. Camptothecin in sterically stabilized phospholipid micelles: a novel nanomedicine. Nanomedicine. 1: 77-84 (2005).

Kreyling WG, Semmler-Behnke M, Möller W. Health implications of nanoparticles. J. Nanopart. Res. 8: 543-562 (2006).

Krishnadas A, Rubinstein I, Onyuksel H. Sterically stabilized phospholipid mixed micelles: in-vitro evaluation as a novel carrier for water-insoluble drugs. Pharm Res. 20: 297-302 (2003).

Kumar C. Nanomaterials for Medical Diagnosis and Therapy, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007.

Kurath M, Maasen S. Toxicology as a nanoscience?-disciplinary identities reconsidered. Part Fibre Toxicol. 3: 6 (2006).

Lanone S, Boczkowski J. Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. Curr. Mol. Med. 6: 651-663 (2006).

Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J Control Release.103: 405-418 (2005).

Liu A, Sun K, Yang J, Zhao D. Toxicological effects of multi-wall carbon nanotubes in rats. J. Nanopart. Res. 10: 1303-1307 (2008).

Liu Z, Davis C, Cai W, He L, Chen X, Dai H. Circulation and long-term fate of functionalized biocompatible single-walled carbon nanotubes inmice probed by Raman spectroscopy. Proc. Natl. Acad. Sci. U. S. A. 105: 1410-1415 (2008).

Malik N, Evagorou EG, Duncan R. Dendrimer-platinate: a novel approach to cancer chemotherapy. Anti-Cancer Drugs. 10: 767–776 (1999).

Matsumura Y, Hamaguchi T, Ura T, Muro K, Yamada Y, Shimada Y, et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 91: 1775- 1781 (2004).

Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labeling and sensing. Nat Mater. 4: 435-446 (2005).

Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. FASEB J. 19: 311–330 (2005).

Murdock RC, Braydich-Stolle L, Schrand AM, Schlager JJ, Hussain SM. Characterization of nanomaterial dispersion in solution prior to in-vitro exposure using dynamic light scattering technique. Toxicol. Sci. 101: 239-253 (2008).

Neerman MF, Zhang W, Parrish AR, Simanek EE. In-vitro and in-vivo evaluation of a melamine dendrimer as a vehicle for drug delivery. Int. J. Pharm. 281: 129-132 (2004).

Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113: 823-839 (2006).

Oberdorster GE, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect. 113: 823-839 (2005).

Pisanic II TR, Blackwell JD, Shubayev VI, Finones RR, Jin S. Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. Biomaterials. 28: 2572-2581 (2007).

Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, Stone V, Brown S, Macnee W, Donaldson K. Carbon nanotubes introduced into the abdominal cavity of mice showasbestos-like pathogenicity in a pilot study. Nat.Nanotechnol. 3: 423–428 (2008).

Powers KW, Brown SC, Krishna VB, Wasdo SC, Moudgil BM, Roberts SM. Research strategies for safety evaluation of nanomaterials. part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol. Sci. 90: 296-303 (2006).

Powers KW, Palazuelos M, Moudgil BM, Roberts SM. Characterization of the size, shape, and state of dispersion of nanoparticles for toxicological studies. Nanotoxicology. 1: 42- 51 (2007).

Rahman I, Biswas SK, Jimenez LA, Torres M, Forman HJ. Glutathione, stress responses, and redox signaling in lung inflammation, Antioxid. Redox Signal. 7: 42–59 (2005).

Rahman I. Regulation of nuclear factor-κB, activator protein-1, and glutathione levels by tumor necrosis factor-α and dexamethasone in alveolar epithelial cells. Biochem. Pharmacol. 60: 1041–1049 (2000).

Rejman J, Oberle V, Zuhorn IS, Hoekstra D. Size-dependent internalization of particles via the pathways of clarthrin- and caveolae-mediated endocytosis. Biochem. J. 377: 159–169 (2004).

Roberts JC, Bhalgat MK, Zera RT. Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst(TM) dendrimers. J. Biomed. Mater. Res. 30: 53–65 (1996).

Ryman-Rasmussen JP, Riviere JE. Monteiro-Riviere NA. Variables influencing interactions of untargeted quantum dot nanoparticles with skin cells and identification of biochemical modulators. Nano Lett. 7: 1344-1348 (2007).

Sayes CM, Reed KL, Warheit DB. Assessing toxicity of fine and nanoparticles: comparing in-vitro measurements to in-vivo pulmonary toxicity profiles. Toxicol. Sci. 97: 163-180 (2007).

Service RF. Nanotoxicology. Nanotechnology grows up. Science. 304: 1732-1734 (2004).

Singh R, Pantarotto D, Lacerda L, Pastorin G, Klumpp C, Prato M, Bianco A, Kosterlos K. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proc. Natl. Acad. Sci. U. S. A. 103: 3357-3362 (2006).

Sonavane G, Tomoda K, Makino K. Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf., B Biointerfaces. 66: 274-280 (2008).

Studart AR, Amstad E, Gauckler LJ. Colloidal stabilization of nanoparticles in concentrated suspensions. Langmuir. 23: 1081-1090 (2007).

Unfried K, C. Albrecht C, Klotz LO, Mikecz AV, S. Grether-Beck S, Schins RPF. Cellular response to nanoparticles: target structures and mechanisms. Nanotoxicology. 1: 52-71 (2007).

Voura EB, Jaiswal JK, Mattoussi H, Simon SM. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat Med. 10: 993-998 (2004).

Wang H, Wang J, Deng X, Sun H, Shi Z, Gu Z, Liu Y, Zhao Y. Biodistribution of carbon single-walled carbon nanotubes in mice. J. Nanosci. Nanotechnol. 4: 1019-1024 (2004).

Yang RS, Chang LW, Wu JP, Tsai MH, Wang HJ, Kuo YC, Yeh TK, Yang CS, Lin P. Persistent tissue kinetics and redistribution of nanoparticles., quantum dot 705, in mice: ICP-MS quantitative assessment. Environ. Health Perspect. 115: 1339-1343 (2007).

Yang S, 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. 181: 182–189 (2008).

Yang SC, Lu LF, Cai Y, Zhu JB, Liang BW, Yang CZ. Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. J Control Release. 59: 299-307 (1999).

Yang ST, Guo W, Lin Yi, Deng XY, Wang HF, Sun HF, Liu YF, Wang X, Wang W, Chen M, Huang YP, Sun YP. Biodistribution of pristine single-walled carbon nanotubes in-vivo. J. Phys. Chem. 111: 17761–17764 (2007).

Zara GP, Cavalli R, Bargoni A, Fundaro A, Vighetto D, Gasco MR. Intravenous administration to rabbits of non-stealth and stealth doxorubicin-loaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other tissues. J Drug Target. 10: 327-335 (2002).

Zhu MT, Feng WY, Wang B, Wang TC, Gu YQ, Wang M, Wang Y, Ouyang H, Zhao YL, Chai ZF. Comparative study of pulmonary responses to nano- and submicron-sized ferric oxide in rats. Toxicology. 247: 102–111 (2008).