Skip to main content
SpringerLink
Log in

PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD50(14) of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD50(14) of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  • Adamson I, Sienko A, Tenenbein M (1993) Pulmonary toxicity of deferoxamine in iron poisoned mice. Toxicol Appl Pharmacol 120:13–19. doi:10.1006/taap.1993.1081

    Article  Google Scholar 

  • Al Faraj A (2013) Preferential magnetic nanoparticle uptake by bone marrow derived macrophages sub-populations: effect of surface coating on polarization, toxicity, and in vivo MRI detection. J Nanopart Res 15:1. doi:10.1007/s11051-013-1797-9

    Article  Google Scholar 

  • Alarifi S, Ali D, Alkahtani S, Alhader M (2014) Iron oxide nanoparticles induce oxidative stress, DNA damage, and caspase activation in the human breast cancer cell line. Biol Trace Elem Res 159:416–424. doi:10.1007/s12011-014-9972-0

    Article  Google Scholar 

  • Ankamwar B, Lai T, Huang J, Liu R, Hsiao M, Chen C, Hwu Y (2010) Biocompatibility of Fe3O4 nanoparticles evaluated by in vitro cytotoxicity assays using normal, glia and breast cancer cells. Nanotechnology 21:075102. doi:10.1088/0957-4484/21/7/075102

    Article  Google Scholar 

  • Archana P, Rao BN, Ballal M, Rao BS (2009) Thymol, a naturally occurring monocyclic dietary phenolic compound protects Chinese hamster lung fibroblasts from radiation-induced cytotoxicity. Mutat Res 680:70–77. doi:10.1016/j.mrgentox.2009.09.010

    Article  Google Scholar 

  • Auffan M et al (2008) Relation between the redox state of iron-based nanoparticles and their cytotoxicity toward Escherichia coli. Environ Sci Technol 42:6730–6735. doi:10.1021/es800086f

    Article  Google Scholar 

  • Baalousha M (2009) Aggregation and disaggregation of iron oxide nanoparticles: influence of particle concentration, pH and natural organic matter. Sci Total Environ 407:2093–2101. doi:10.1016/j.scitotenv.2008.11.022

    Article  Google Scholar 

  • Balakumaran A, Pawelczyk E, Ren J, Sworder B, Chaudhry A, Sabatino M, Stroncek D, Frank JA, Robey PG (2010) Superparamagnetic iron oxide nanoparticles labeling of bone marrow stromal (mesenchymal) cells does not affect their “stemness”. PLoS ONE 5:e11462. doi:10.1371/journal.pone.0011462

    Article  Google Scholar 

  • Barhoumi L, Dewez D (2013) Toxicity of superparamagnetic iron oxide nanoparticles on green alga Chlorella vulgaris. Biomed Res Int 2013:647974. doi:10.1155/2013/647974

    Article  Google Scholar 

  • Baroli B, Ennas MG, Loffredo F, Isola M, Pinna R, López-Quintela MA (2007) Penetration of metallic nanoparticles in human full-thickness skin. J Invest Dermatol 127:1701–1712. doi:10.1038/sj.jid.5700733

    Google Scholar 

  • Barrera C, Herrera AP, Rinaldi C (2009) Colloidal dispersions of monodisperse magnetite nanoparticles modified with poly (ethylene glycol). J Colloid Interface Sci 329:107–113. doi:10.1016/j.jcis.2008.09.071

    Article  Google Scholar 

  • Bellin MF, Beigelman C, Precetti-Morel S (2000) Iron oxide-enhanced MR lymphography: initial experience. Eur J Radiol 34:257–264. doi:10.1016/S0720-048X(00)00204-7

    Article  Google Scholar 

  • Berry CC, Wells S, Charles S, Curtis AS (2003) Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro. Biomaterials 24:4551–4557. doi:10.1016/S0142-9612(03)00237-0

    Article  Google Scholar 

  • Bhasin G, Kauser H, Athar M (2002) Iron augments stage-I and stage-II tumor promotion in murine skin. Cancer Lett 183:113–122. doi:10.1016/S0304-3835(02)00116-7

    Article  Google Scholar 

  • Brown DM, Hutchison L, Donaldson K, Stone V (2007) The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells: modulating effects of calcium-signaling antagonist. Am J Physiol Lung Cell Mol Physiol 292:L1444–L1451. doi:10.1152/ajplung.00162.2006

    Article  Google Scholar 

  • Brullot W, Reddy NK, Wouters J, Valev VK, Goderis B, Vermant J, Verbiest T (2012) Versatile ferrofluids based on polyethylene glycol coated iron oxide nanoparticles. J Magn Magn Mater 324:1919–1925. doi:10.1016/j.jmmm.2012.01.032

    Article  Google Scholar 

  • Brunner TJ, Wick P, Manser P, Spohn P, Grass RN, Limbach LK, Bruinink A, Stark WJ (2006) In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 40:4374–4381. doi:10.1021/es052069i

    Article  Google Scholar 

  • Bulte JW, Douglas T, Witwer B, Zhang S-C, Strable E, Lewis BK, Zywicke H, Miller B, van Gelderen P, Moskowitz BM (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19:1141–1147. doi:10.1038/nbt1201-1141

    Article  Google Scholar 

  • Buyukhatipoglu K, Miller T, Morss Clyne A (2009) Flame synthesis and in vitro biocompatibility assessment of superparamagnetic iron oxide nanoparticles: cellular uptake, toxicity and proliferation studies. J Nanosci Nanotechnol 9:6834–6843. doi:10.1166/jnn.2009.1477

    Article  Google Scholar 

  • Chen BA, Jin N, Wang J, Ding J, Gao C, Cheng J, Xia G, Gao F, Zhou Y, Chen Y, Zhou G, Li X, Zhang Y, Tang M, Wang X (2010) The effect of magnetic nanoparticles of Fe3O4 on immune function in normal ICR mice. Int J Nanomed 5:593. doi:10.2147/IJN.S12162

    Article  Google Scholar 

  • Cho WS, Cho M, Kim SR, Choi M, Lee JY, Han BS, Park SN, Yu MK, Jon S, Jeong J (2009) Pulmonary toxicity and kinetic study of Cy5. 5-conjugated superparamagnetic iron oxide nanoparticles by optical imaging. Toxicol Appl Pharmacol 239:106–115. doi:10.1016/j.taap.2009.05.026

    Article  Google Scholar 

  • Cho WS, Duffin R, Thielbeer F, Bradley M, Megson IL, MacNee W, Poland CA, Tran CL, Donaldson K (2012) Zeta potential and solubility to toxic ions as mechanisms of lung inflammation caused by metal/metal-oxide nanoparticles. Toxicol Sci 126:469–477. doi:10.1093/toxsci/kfs006

    Article  Google Scholar 

  • DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Kenneth HY, Yeo CJ, Calhoun ES (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475:106–109. doi:10.1038/nature10189

    Article  Google Scholar 

  • Dick CA, Brown DM, Donaldson K, Stone V (2003) The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol 15:39–52. doi:10.1080/08958370304454

    Article  Google Scholar 

  • Drexler KE (2006) Engines of creation 2.0 The coming era of nanotechnology, WOWIO, e-book edition Cerca con Google

  • Du B, Han S, Li H, Zhao F, Su X, Cao X, Zhang Z (2015) Multi-functional liposomes showing radiofrequency-triggered release and magnetic resonance imaging for tumor multi-mechanism therapy. Nanoscale 7:5411–5426. doi:10.1039/c4nr04257c

    Article  Google Scholar 

  • Easo SL, Mohanan PV (2015) In vitro hematological and in vivo immunotoxicity assessment of dextran stabilized iron oxide nanoparticles. Coll Surf B Biointerfaces 134:122–130. doi:10.1016/j.colsurfb.2015.06.046

    Article  Google Scholar 

  • Elias A, Tsourkas A (2009) Imaging circulating cells and lymphoid tissues with iron oxide nanoparticles. Hematol Am Soc Hematol Educ Progr 2009:720–726. doi:10.1182/asheducation-2009.1.720

    Article  Google Scholar 

  • Ferin J, Oberdorster G, Penney DP (1992) Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol 6:535–542. doi:10.1165/ajrcmb/6.5.535

    Article  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. doi:10.1038/35041687

    Article  Google Scholar 

  • Ganasoundari A, Devi PU, Rao B (1998) Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum. Mutat Res 397:303–312. doi:10.1016/S0027-5107(97)00230-3

    Article  Google Scholar 

  • Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021. doi:10.1016/j.biomaterials.2004.10.012

    Article  Google Scholar 

  • Hamley IW (2003) Nanotechnology with soft materials Angew. Chem Int Ed 42:1692–1712. doi:10.1002/anie.200200546

    Article  Google Scholar 

  • Huang J, Bu L, Xie J, Chen K, Cheng Z, Li X, Chen X (2010) Effects of nanoparticle size on cellular uptake and liver MRI with polyvinylpyrrolidone-coated iron oxide nanoparticles. ACS Nano 4:7151–7160. doi:10.1021/nn101643u

    Article  Google Scholar 

  • Hussain S, Hess K, Gearhart J, Geiss K, Schlager J (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983. doi:10.1016/j.tiv.2005.06.034

    Article  Google Scholar 

  • Jain TK, Reddy MK, Morales MA, Leslie-Pelecky DL, Labhasetwar V (2008) Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol Pharm 5:316–327. doi:10.1021/mp7001285

    Article  Google Scholar 

  • Jeng HA, Swanson J (2006) Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A Tox Hazard Subst Environ Eng 41:2699–2711. doi:10.1080/10934520600966177

    Article  Google Scholar 

  • Jokerst JV, Lobovkina T, Zare RN, Gambhir SS (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond) 6:715–728. doi:10.2217/nnm.11.19

    Article  Google Scholar 

  • Karlsson HL, Holgersson Å, Möller L (2008) Mechanisms related to the genotoxicity of particles in the subway and from other sources. Chem Res Toxicol 21:726–731. doi:10.1021/tx7003568

    Article  Google Scholar 

  • Kedziorek DA, Muja N, Walczak P, Ruiz-Cabello J, Gilad AA, Jie CC, Bulte JW (2010) Gene expression profiling reveals early cellular responses to intracellular magnetic labeling with superparamagnetic iron oxide nanoparticles. Magn Reson Med 63:1031–1043. doi:10.1002/mrm.22290

    Article  Google Scholar 

  • Kim JS, Yoon TJ, Yu KN, Kim BG, Park SJ, Kim HW, Lee KH, Park SB, Lee JK, Cho MH (2006) Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicol Sci 89:338–347. doi:10.1093/toxsci/kfj027

    Article  Google Scholar 

  • Kumar R, Inbaraj BS, Chen B (2010) Surface modification of superparamagnetic iron nanoparticles with calcium salt of poly (γ-glutamic acid) as coating material. Mater Res Bull 45:1603–1607. doi:10.1016/j.materresbull.2010.07.017

    Article  Google Scholar 

  • Kumari M, Rajak S, Singh SP, Kumari SI, Kumar PU, Murty US, Mahboob M, Grover P, Rahman MF (2012) Repeated oral dose toxicity of iron oxide nanoparticles: biochemical and histopathological alterations in different tissues of rats. J Nanosci Nanotechnol 12:2149–2159. doi:10.1166/jnn.2012.5796

    Article  Google Scholar 

  • Kumari M, Rajak S, Singh SP, Murty US, Mahboob M, Grover P, Rahman MF (2013) Biochemical alterations induced by acute oral doses of iron oxide nanoparticles in Wistar rats. Drug Chem Toxicol 36:296–305. doi:10.3109/01480545.2012.720988

    Article  Google Scholar 

  • Kwon JT, Hwang SK, Jin H, Kim DS, Minai Tehrani A, Yoon HJ, Choi M, Yoon TJ, Han DY, Kang YW (2008) Body distribution of inhaled fluorescent magnetic nanoparticles in the mice. J Occup Health 50:1–6. doi:10.1539/joh.50.1

    Article  Google Scholar 

  • Larsen EK, Nielsen T, Wittenborn T, Birkedal H, Vorup Jensen T, Jakobsen MH, Ostergaard L, Horsman MR, Besenbacher F, Howard KA, Kjems J (2009) Size-dependent accumulation of PEGylated silane-coated magnetic iron oxide nanoparticles in murine tumors. ACS Nano 3:1947–1951. doi:10.1021/nn900330m

    Article  Google Scholar 

  • Leonard A, Lauwerys R (1980) Carcinogenicity and mutagenicity of chromium. Mutat Res 76:227–239. doi:10.1016/0165-1110(80)90018-4

    Article  Google Scholar 

  • Lewinski N, Graczyk H, Riediker M (2013) Human inhalation exposure to iron oxide particles. Bio Nano Mat 14:5–23. doi:10.1515/bnm-2013-0007

    Google Scholar 

  • Limbach LK, Li Y, Grass RN, Brunner TJ, Hintermann MA, Muller M, Gunther D, Stark WJ (2005) Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. Environ Sci Technol 39:9370–9376. doi:10.1021/es051043o

    Article  Google Scholar 

  • Limbach LK, Wick P, Manser P, Grass RN, Bruinink A, Stark WJ (2007) Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress. Environ Sci Technol 41:4158–4163. doi:10.1021/es062629t

    Article  Google Scholar 

  • Luo C, Li Y, Yang L, Wang X, Long J, Liu J (2014) Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses. Arch Toxicol 89:357–369. doi:10.1007/s00204-014-1267-x

    Article  Google Scholar 

  • Mahmoudi M, Laurent S, Shokrgozar MA, Hosseinkhani M (2011a) Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell “vision” versus physicochemical properties of nanoparticles. ACS Nano 5:7263–7276. doi:10.1021/nn2021088

    Article  Google Scholar 

  • Mahmoudi M, Sant S, Wang B, Laurent S, Sen T (2011b) Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliv Rev 63:24–46. doi:10.1016/j.addr.2010.05.006

    Article  Google Scholar 

  • Mahmoudi M, Simchi A, Imani M, Milani AS, Stroeve P (2009) An in vitro study of bare and poly (ethylene glycol)-co-fumarate-coated superparamagnetic iron oxide nanoparticles: a new toxicity identification procedure. Nanotechnology 20:225104. doi:10.1088/0957-4484/20/22/225104

    Article  Google Scholar 

  • Mesárošová M, Kozics K, Babelova A, Regendova E, Pastorek M, Vnukova D, Buliakova B, Razga F, Gabelova A (2014) The role of reactive oxygen species in the genotoxicity of surface-modified magnetite nanoparticles. Toxicol Lett 226:303–313. doi:10.1016/j.toxlet.2014.02.025

    Article  Google Scholar 

  • Moller P, Jacobsen NR, Folkmann JK, Danielsen PH, Mikkelsen L, Hemmingsen JG, Vesterdal LK, Forchhammer L, Wallin H, Loft S (2010) Role of oxidative damage in toxicity of particulates. Free Radic Res 44:1–46. doi:10.3109/10715760903300691

    Article  Google Scholar 

  • Nance EA, Woodworth GF, Sailor KA, Shih TY, Xu Q, Swaminathan G, Xiang D, Eberhart C, Hanes J (2012) A dense poly(Ethylene Glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci Transl Med 4:149ra119. doi:10.1126/scitranslmed.3003594

    Article  Google Scholar 

  • Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627. doi:10.1126/science.1114397

    Article  Google Scholar 

  • Owens DE III, Peppas NA (2006) Opsonization, biodistribution and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102. doi:10.1016/j.ijpharm.2005.10.010

    Article  Google Scholar 

  • Park S, Lim J, Kim J, Yun H, Kim C (2006) Toxicity estimation of magnetic fluids in a biological test. J Magn Magn Mater 304:e406–e408. doi:10.1016/j.jmmm.2006.01.205

    Article  Google Scholar 

  • Park Y, Whitaker RD, Nap RJ, Paulsen JL, Mathiyazhagan V, Doerrer LH, Song YQ, Hürlimann MD, Szleifer I, Wong JY (2012) Stability of superparamagnetic iron oxide nanoparticles at different pH values: experimental and theoretical analysis. Langmuir 28:6246–6255. doi:10.1021/la204628c

    Article  Google Scholar 

  • Puntarulo S (2005) Iron, oxidative stress and human health. Mol Aspects Med 26:299–312. doi:10.1016/j.mam.2005.07.001

    Article  Google Scholar 

  • Qian L, Meng T, Ming M, Ning G (2005) Study on cytotoxicity and oxidative effects of different sizes of hematite (Fe2O3) nanoparticles on CHL cell in vitro. China J Mod Med 13:001

    Google Scholar 

  • Randhawa MA (2009) Calculation of LD50 values from the method of Miller and Tainter, 1944. J Ayub Med Coll Abbottabad 21:184–185

    Google Scholar 

  • Rao BN, Rao BS, Aithal BK, Kumar MS (2009) Radiomodifying and anticlastogenic effect of Zingerone on Swiss albino mice exposed to whole body gamma radiation. Mutat Res 677:33–41. doi:10.1016/j.mrgentox.2009.05.004

    Article  Google Scholar 

  • Reichard JF, Motz GT, Puga A (2007) Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucl Acids Res 35:7074–7086. doi:10.1093/nar/gkm638

    Article  Google Scholar 

  • Schwegmann H, Feitz AJ, Frimmel FH (2010) Influence of the zeta potential on the sorption and toxicity of iron oxide nanoparticles on S. cerevisiae and E. coli. J Colloid Interface Sci 347:43–48. doi:10.1016/j.jcis.2010.02.028

    Article  Google Scholar 

  • Singh N (2009) Conference scene-nanotoxicology: health and environmental impacts. Nanomedicine 4:385–390. doi:10.2217/nnm.09.20

    Article  Google Scholar 

  • Singh N, Jenkins GJ, Asadi R, Doak SH (2010) Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev 1:5358. doi:10.3402/nano.v1i0.5358

    Article  Google Scholar 

  • Smith MT (1996) The mechanism of benzene-induced leukemia: a hypothesis and speculations on the causes of leukemia. Environ Health Perspect 6:1219–1225

    Article  Google Scholar 

  • Soenen SJ, De Cuyper M (2010) Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects. Nanomedicine 5:1261–1275. doi:10.2217/nnm.10.106

    Article  Google Scholar 

  • Stumm W, Morgan JJ (1996) Aquatic chemistry: chemical equilibria and rates in natural waters. Wiley interscience, New York

    Google Scholar 

  • Thomas DJ, Styblo M, Lin S (2001) The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol 176:127–144. doi:10.1006/taap.2001.9258

    Article  Google Scholar 

  • Unfried K, Albrecht C, Klotz LO, Von Mikecz A, Grether-Beck S, Schins RPF (2007) Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicology 1:52–71. doi:10.1080/00222930701314932

    Article  Google Scholar 

  • Wahajuddin SA (2012) Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int J Nanomed 7:3445. doi:10.2147/IJN.S30320

    Article  Google Scholar 

  • Wang L, Wang L, Ding W, Zhang F (2010) Acute toxicity of ferric oxide and zinc oxide nanoparticles in rats. J Nanosci Nanotechnol 10:8617–8624. doi:10.1166/jnn.2010.2483

    Article  Google Scholar 

  • Xie J, Liu G, Eden HS, Ai H, Chen X (2011) Surface-engineered magnetic nanoparticle platforms for cancer imaging and therapy. Acc Chem Res 44:883–892. doi:10.1021/ar200044b

    Article  Google Scholar 

  • Yang L, Kuang H, Zhang W, Aguilar ZP, Xiong Y, Lai W, Xu H, Wei H (2015) Size dependent biodistribution and toxicokinetics of iron oxide magnetic nanoparticles in mice. Nanoscale 7:625–636. doi:10.1039/C4NR05061D

    Article  Google Scholar 

  • Zhao S, Lin X, Zhang L, Sun L, Li J, Yang W, Sun Z (2012) The in vivo investigation of Fe3O4-nanoparticles acute toxicity in mice. BME 24:229–235. doi:10.4015/S1016237212500056

    Google Scholar 

  • Zhu MT, Feng WY, Wang B, Wang TC, Gu YQ, Wang M, Wang Y, Ouyang H, Zhao YL, Chai ZF (2008) Comparative study of pulmonary responses to nano-and submicron-sized ferric oxide in rats. Toxicology 247:102–111. doi:10.1016/j.tox.2008.02.011

    Article  Google Scholar 

Website references

Download references

Acknowledgments

The authors gratefully acknowledge the support and encouragement of Prof. K. Satyamoorthy, Director, School of Life Sciences and Manipal University for providing with laboratory facilities and financial support. The authors are thankful to Mr Srinivasa Kumar N. Acharya, Assistant Professor Manipal Centre for European Studies and an advisor for Manipal University Press and Dr. T.G. Vasudevan, Assistant Professor, School of Life Sciences, Manipal University for their editorial assistance. The authors are also grateful to Mrs. Vineeta Sawant and Mr. Prashanth of Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai for their assistance in TEM analysis, Dr. Girish Kunte, CeNSE, IISc, Bangalore for AFM analysis, also Dr. Sundaresan Athinarayanan and Mr. Chandan De of Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore for their assistance in Magnetization measurements.

Author information

Authors and Affiliations

  1. Department of Radiation Biology & Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, 576 104, India

    Suma Prabhu & Bola Sadashiva Satish Rao

  2. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, 576 104, India

    Srinivas Mutalik

  3. Department of Pathology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, 575 001, India

    Sharada Rai

  4. Director - Research (Health Sciences), Manipal University, Manipal, Karnataka, 576104, India

    Nayanabhirama Udupa

Authors
  1. Suma Prabhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Srinivas Mutalik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharada Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nayanabhirama Udupa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bola Sadashiva Satish Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bola Sadashiva Satish Rao.

Ethics declarations

Conflict of Interest

None declared.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prabhu, S., Mutalik, S., Rai, S. et al. PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study. J Nanopart Res 17, 412 (2015). https://doi.org/10.1007/s11051-015-3216-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-015-3216-x

Keywords

Search

Navigation