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Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran–spermine nanoparticle system

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Abstract

This study aims to fabricate and formulate a new magnetic resonance imaging (MRI) contrast agent based on a dextran–spermine nanoparticulate system loaded with super paramagnetic iron oxide nanoparticles (SPION). SPION-loaded spermine–dextran nanoparticles were prepared according to a procedure based on the ionic gelation of dextran–spermine with sodium tripolyphosphate (TPP) anions. The effects of process parameters such as pH, concentration of spermine dextran, TPP to dextran–spermine and SPION to dextran–spermine weight ratios, and TPP addition rate were fully investigated to find the optimized formulation through the response surface methodology. At the optimum condition, 75% of the magnetic iron oxide nanoparticles added to the polymeric solution were entrapped in dextran–spermine nanoparticles. Samples were investigated by transmission electron microscopy. The mean particle size of the nanoparticles determined by particle size analyzer was found to be 65 nm at the optimum condition with zeta potential of +90 mV. The SPION-loaded dextran–spermine nanoparticle formulation has the same superparamagnetic properties as SPIONs and at same iron concentration the saturation magnetization (Ms) of the SPION-loaded dextran–spermine nanoparticles was larger than SPIONs. In vitro MRI was performed with gradient echo and spin-echo sequences at 1.5 T. By increasing of iron concentration, the T 2 relaxation times were reduced. Thus, indicating that the saturation magnetization and r 2 and \( r_{2}^{*} \) relaxivities were enhanced, and the contrast effects were improved in comparison to commercial SPIONs.

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References

  1. Chandrasekharan P, Maity D, Chang Tong Y, Kai Hsiang C, Ding J, Si Shen F (2010) Superparamagnetic iron oxide-loaded poly (lactic acid)–d-α-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent. Biomaterials 31:5588–5597

    Article  Google Scholar 

  2. Arruebo M, Fernández Pacheco R, Ricardo Ibarra M, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nano Today 3:23–32

    Google Scholar 

  3. Hamoudeh M, Fessi H (2006) Preparation, characterization and surface study of poly-epsilon caprolactone magnetic microparticles. J Colloid Interface Sci 300:584–590

    Article  CAS  Google Scholar 

  4. Neves AA, Brindle KM (2006) Assessing responses to cancer therapy using molecular imaging. Biochim Biophys Acta 1766:242–261

    CAS  Google Scholar 

  5. Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499

    Article  CAS  Google Scholar 

  6. Moore A, Marecos E, Bogdanov A, Weissleder R (2000) Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model. Radiology 214:568–574

    CAS  Google Scholar 

  7. Himmelreich U, Hoehn M (2008) Stem cell labeling for magnetic resonance imaging. Minim Invasive Ther 17:132–142

    Article  Google Scholar 

  8. Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ, Price J, Hodegs H (2002) Tracking transplanted stem cell migration using bifunctional contrast agent-enhanced magnetic resonance imaging. Neuroimage 17:803–811

    Article  Google Scholar 

  9. Kustermann E, Himmelreich U, Kandal K, Geelen T, Ketkar A, Wiedermann D, Strecker C, Esser J, Arnhold S, Hoehn M (2008) Efficient stem cell labeling for MRI studies. Contrast Media Mol Imaging 3:27–37

    Article  CAS  Google Scholar 

  10. Weissleder R, Bogdanov A, Neuwelt EA, Papisov M (1995) Long-circulating iron oxides for MR imaging. Adv Drug Deliv Rev 16:321–334

    Article  CAS  Google Scholar 

  11. Liu H, Li J (2010) Preparation and characterization of poly (PEGMA) modified superparamagnetic nanogels used as potential MRI contrast agents. Iran Polym J 17(9):721–727

    Google Scholar 

  12. Briley-Saebo K, Bjørnerud A, Grant D, Ahlstrom H, Berg T, Kindberg GM (2004) Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging. Cell Tissue Res 316:315–323

    Article  CAS  Google Scholar 

  13. Chertok B, David AE, Yang VC (2008) Delivery of functional proteins to brain tumor using MRI-monitored magnetically targeted nanoparticles. J Control Release 132:e61–e62

    Article  CAS  Google Scholar 

  14. Dias AMGC, Hussain A, Marcos AS, Roque ACA (2011) A biotechnological perspective on the application of iron oxide magnetic colloids modified with polysaccharides. Biotechnol Adv 29:142–155

    Article  CAS  Google Scholar 

  15. Villa C, Erratico S, Razini P, Fiori F, Rustichelli F, Torrente Y, Belicchi M (2010) Stem cell tracking by nanotechnologies. Int J Mol Sci 11:1070–1081

    Article  CAS  Google Scholar 

  16. Bulte JW, Arbab AS, Douglas T, Frank JA (2004) Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. Method Enzymol 386:275–299

    Article  CAS  Google Scholar 

  17. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:404–410

    Google Scholar 

  18. Boyer C, Whittaker MR, Bulmus V, Liu J, Davis TP (2010) The design and utility of polymer stabilized iron oxide nanoparticles for nanomedicine applications. NPG Asia Mater 2:23–30

    Article  Google Scholar 

  19. Kim D, Hong KS, Song J (2007) The present status of cell tracking methods in animal models using magnetic resonance imaging technology. Mol Cells 23:132–137

    CAS  Google Scholar 

  20. Kaim AH, Wischer T, O’Reilly T, Jundt G, Fröhlich J, Schulthess GK, Allegrini PR (2002) MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats. Radiology 225:808–814

    Article  Google Scholar 

  21. Jung CW, Jacobs P (1995) Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging 13:661–674

    Article  CAS  Google Scholar 

  22. Mody VV, Nounou MI, Bikram M (2009) Novel nanomedicine-based MRI contrast agents for gynecological malignancies. Adv Drug Deliv Rev 61:795–807

    Article  CAS  Google Scholar 

  23. Strable E, Bulte JM, Moskowitz B, Vivekanandan K, Allen M, Douglas T (2001) Synthesis and characterization of soluble iron oxide-dendrimer composites. Chem Mater 13:2201–2209

    Article  CAS  Google Scholar 

  24. Kohler N, Sun C, Fichtenholtz A, Gunn J, Fang C, Zhang MQ (2006) Methotrexate-immobilized poly (ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. Small 2:785–792

    Article  CAS  Google Scholar 

  25. Liu HL, Ko SP, Wu JH, Jung MH, Min JH, Lee JH, An DH, Kim YK (2007) One-pot polyol synthesis of mono size PVP-coated sub-5 nm Fe3O4 nanoparticles for biomedical applications. J Magn Magn Mater 310:815–817

    Article  Google Scholar 

  26. Lee HY, Lee SH, Xu C, Xie J, Lee JH, Wu B, Koh AL, Wang X, Sinclair R, Wang SX, Nishimura DG, Biswal S, Sun S, Cho SH, Chen X (2008) Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent. Nanotechnology 19:1–6

    Google Scholar 

  27. Arsalani N, Fattahi H, Nazarpoor M (2010) Synthesis and characterization of PVP-functionalized superparamagnetic Fe3O4 nanoparticles as an MRI contrast agent. eXPRESS Polym Lett 6:329–338

    Article  Google Scholar 

  28. Wang Y, Woon NY, Chen Y, Shuter B, Yi J, Ding J, Wang SC, Sishen F (2008) Formulation of superparamagnetic iron oxides by nanoparticles of biodegradable polymers for magnetic resonance imaging. Adv Funct Mater 18:308–318

    Article  CAS  Google Scholar 

  29. Pich A, Bhattacharya S, Ghosh A, Adler A (2005) Composite magnetic particles: 2. Encapsulation of iron oxide by surfactant-free emulsion polymerization. Polymer 46:4596–4603

    Article  CAS  Google Scholar 

  30. Zheng W, Gao F, Gu H (2005) Magnetic polymer nanospheres with high and uniform magnetite content. J Magn Magn Mater 288:403–410

    Article  CAS  Google Scholar 

  31. Ngaboni Okassa L, Marchais H, Douziech Eyrolles H, Cohen S, Souce M, Dubois P, Chourpa R (2005) Development and characterization of sub-micron poly (d, l-lactide-co-glycolide) particles loaded with magnetite/maghemite nanoparticles. Int J Pharm 302:187–196

    Article  CAS  Google Scholar 

  32. Joumaa N, Toussay P, Lansalot M, Elaissari A (2008) Surface modification of iron oxide nanoparticles by a phosphate-based macromonomer and further encapsulation into submicrometer polystyrene particles by miniemulsion polymerization. J Polym Sci Part A 46:327–340

    Article  CAS  Google Scholar 

  33. Lee SJ, Jeong JR, Shina SC, Kim JC, Changa YH, Chang YM, Kim JD (2004) Nanoparticles of magnetic ferric oxides encapsulated with poly(d, l lactide-co-glycolide) and their applications to magnetic resonance imaging contrast agent. J Magn Magn Mater 272:2432–2433

    Article  Google Scholar 

  34. Sundar S, Kundu J, Kundu SC (2010) Biopolymeric nanoparticles. Sci Technol Adv Mat 11:014104

    Article  Google Scholar 

  35. Yang J, Gunn J, Dave SR, Zang M, Wang YA, Gao X (2008) Ultrasensitive detection and molecular imaging with magnetic nanoparticles. Analyst 133:154–160

    Article  CAS  Google Scholar 

  36. Azzam T, Eliyahu H, Shapira L, Linial M, Barenholz Y, Domb AJ (2002) Polysaccharide–oligoamine based conjugates for gene delivery. J Med Chem 45:1817–1824

    Article  CAS  Google Scholar 

  37. Abedini F, Ismail M, Hosseinkhani H, Azmi T, Omarb A, PeiPei C, Ismail N, Farber I, Domb AJ (2010) Toxicity evaluation of dextran–spermine polycation as a tool for gene therapy in vitro. J Cell Anim Biol 4:170–176

    CAS  Google Scholar 

  38. Liu F, Huang L (2002) Development of non-viral vectors for systemic gene delivery. J Control Release 78:259–266

    Article  CAS  Google Scholar 

  39. Hosseinkhani H, Azzam T, Kobayashi H, Hiraoka Y, Shimokawa H, Domb AJ, Tabata Y (2006) Combination of 3-D tissue engineered scaffold and non-viral gene enhance in vitro DNA expression of mesenchymal stem cells. Biomaterials 27:4269–4278

    Article  CAS  Google Scholar 

  40. Hosseinkhani H, Inatsugu Y, Hiraoka Y, Inoue S, Shimokawa H, Tabata Y (2005) Impregnation of plasmid DNA into three-dimensional scaffolds and medium perfusion enhance in vitro DNA expression of mesenchymal stem cells. Tissue Eng 11:1459–1475

    Article  CAS  Google Scholar 

  41. Hosseinkhani H, Inatsugu Y, Inoue S, Hiraoka Y, Tabata Y (2005) Perfusion culture enhances the osteogenic differentiation of rat mesenchymal stem cells in collagen sponge rein forced with poly (glycolic acid) fiber. Tissue Eng 11:1476–1488

    Article  CAS  Google Scholar 

  42. Hosseinkhani H, Yamamoto M, Inatsugu Y, Hiraoka Y, Inoue S, Shimokawa H, Tabata Y (2006) Enhanced ectopic bone formation using a combination of plasmid DNA impregnation into 3-D scaffold and bioreactor perfusion culture. Biomaterials 27:1387–1398

    Article  CAS  Google Scholar 

  43. Ahmad A, Mukherjee P, Senapati S, Mandal D, Islam Khan M, Kumar R, Sastry M (2003) Extracellular biosynthesis of silver nanoparticles using the fungus Fusarium oxysporum. Colloid Surf B 28:313–318

    Article  CAS  Google Scholar 

  44. Calvo P, Remunan Lopez C, Vila Jata JL, Alonso MJ (1997) Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci 63:125–132

    Article  CAS  Google Scholar 

  45. Katas H, Oya Alpar H (2006) Development and characterization of chitosan nanoparticles for SIRNA delivery. J Control Release 115:216–225

    Article  CAS  Google Scholar 

  46. Hasanzadeh- Kafshgari M, Khorram M, Khodadoost M, Khavari S (2011) Reinforcement of chitosan nanoparticles obtained by an ionic cross-linking process. Iran Polym J 20(5):445–456

    Google Scholar 

  47. Lin KF, Hsu CY, Huang TS, Chiu WY, Lee YH, Young TH (2005) A novel method to prepare chitosan/montmorillonite nanocomposites. J Appl Polym Sci 98(5):2042–2047

    Article  CAS  Google Scholar 

  48. Gan Q, Wang T, Cochrane T, Mccarron P (2005) Modulation of surface charge, particle size and morphological properties of chitosan–TPP nanoparticles intended for gen delivery. Colloid Surf B 44:65–73

    Article  CAS  Google Scholar 

  49. Kavaz D, Çirak T, Özturk E, Bayram C, Denkba EB (2008) Preparation of magnetic chitosan nanoparticle for biomedical diverse applications. NATO Sci Peace Secur 2:313–320

    Google Scholar 

  50. Hashemi-Najafabadi S, Vasheghani-Farahani E, Shojaosadati SA, Rasaee MJ, Moin M, Pourpak Z (2006) Factorial design optimization of red blood cell PEGylation with a low molecular weight polymer. Iran Polym J 15(8):675–683

    CAS  Google Scholar 

  51. Bagheri-Khoulenjani S, Etrati-Khosroshahi M, Mirzadeh H (2010) Particle size and distribution modelling of nanohydroxyapatite-in-gelatin nanocomposite microspheres by surface response method. Iran Polym J 19(10):743–755

    CAS  Google Scholar 

  52. Bhumkar DR, Pokharkar VB (2006) Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: a technical note. AAPS PharmSciTechnol 7:e1–e6

    Google Scholar 

  53. Win KY, Feng SS (2005) Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 26:2713–2722

    Article  CAS  Google Scholar 

  54. Lin CR, Chiang RK, Wang JS, Sung TW (2006) Magnetic properties of mono disperse iron oxide nanoparticles. J Appl Phys 99:710–713

    Google Scholar 

  55. Ai H, Flask C, Weinberg B, Shuai X, Pagel MD, Farrell D, Duerk J, Gao J (2005) Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv Mater 17:1949–1952

    Article  CAS  Google Scholar 

  56. Lu J, Ma S, Sun J, Xia C, Liu C, Wang Z, Zhao X, Gao F, Gong Q, Song B, Shuai X, Ai H, Gu Z (2009) Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging. Biomaterials 30:2919–2928

    Article  CAS  Google Scholar 

  57. Nasongkla N, Bey E, Ren JM, Ai H, Khemtong C, Guthi JS, Chin SF, Sherry D, Boothman DA, Gao J (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6:2427–2430

    Article  CAS  Google Scholar 

  58. Kim EH, Lee HS, Kwak BK, Kim BK (2005) Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent. J Magn Magn Mater 289:328–330

    Article  CAS  Google Scholar 

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Correspondence to Ebrahim Vasheghani-Farahani.

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Mohammad-Taheri, M., Vasheghani-Farahani, E., Hosseinkhani, H. et al. Fabrication and characterization of a new MRI contrast agent based on a magnetic dextran–spermine nanoparticle system. Iran Polym J 21, 239–251 (2012). https://doi.org/10.1007/s13726-012-0027-0

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  • DOI: https://doi.org/10.1007/s13726-012-0027-0

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