Hydrogels-Based Drug Delivery System with Molecular Imaging



Drug delivery systems with molecular imaging capability are usually nanoscopic therapeutic systems that incorporate therapeutic agents and diagnostic imaging probes. ­Polymers (which form hydrogels) and molecular imaging probes used currently were reviewed firstly. ­Polymer-coated molecular imaging probes were also reviewed to introduce the ­basic com­ponent in the preparation of drug delivery systems with molecular imaging capability. Finally, the recent studies on the drug delivery systems with molecular imaging capability were summarized and their prospect was addressed.


Gold Nanoparticles Drug Delivery System Lower Critical Solution Temperature Iron Oxide Nanoparticles Polymeric Micelle 


  1. 1.
    Liu YY, Fan XD (2005) Synthesis, properties and controlled release behaviors of hydrogel networks using cyclodextrin as pendant groups. Biomaterials 26:6367–6374Google Scholar
  2. 2.
    John C, Lev EB, Edmond M (2003) Diffusion and release of solutes in pluronic-g-poly(acrylic acid) hydrogels. Langmuir 19:9162–9172Google Scholar
  3. 3.
    Alvarez-Lorenzoa C, Concheiroa A, Dubovik AS (2005) Temperature-sensitive chitosan-poly(N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties. J Control Release 102:629–641Google Scholar
  4. 4.
    Wang SC, Chen BH, Wang LF et al (2007) Release characteristics of lidocaine from local implant of polyanionic and polycationic hydrogels. J Control Release 118:333–339Google Scholar
  5. 5.
    Dayananda K, He C, Park DK et al (2008) pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane). Polymer 49(23):4968–4973Google Scholar
  6. 6.
    Bhattarai N, Ramay HR, Gunn J et al (2005) PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release. J Control Release 103:609–624Google Scholar
  7. 7.
    Zhang R, Tang M, Bowyer A et al (2005) A novel pH and ionic strength-sensitive carboxymethyl dextran hydrogel. Biomaterials 26:4677–4683Google Scholar
  8. 8.
    Mikos AG, Papadaki MG, Kouvrokoglou S (1994) Mini-review: islet transplantation to create a bioartificial pancreas. Biotechnol Bioeng 43:673–677Google Scholar
  9. 9.
    Laney MW, Kirsten NH, Kathryn H et al (2007) The effects of cell–matrix interactions on encapsulated b-cell function within hydrogels functionalized with matrix-derived adhesive peptides. Biomaterials 28:3004–3011Google Scholar
  10. 10.
    Hou QP, Bae YH (1999) Biohybrid artificial pancreas based on macrocapsule device. Adv Drug Deliv Rev 35:271–287Google Scholar
  11. 11.
    Chun MK, Cho CS, Choi HK (2002) Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization. J Control Release 81:327–334Google Scholar
  12. 12.
    Siegel RA, Falamarzian M, Firestone BA et al (1988) pH controlled release from hydrophobic/polyelectrolyte copolymer hydrogel. J Control Release 8:179–182Google Scholar
  13. 13.
    Moneghini M, Voinovich D, Princivalle F et al (2000) Formulation and evaluation of vinylpyrrolidone/vinylacetate copolymer microspheres with carbamazepine. Pharm Dev Technol 5:347–353Google Scholar
  14. 14.
    Torchilin VP, Shtilman MI, Trubetskoy VS et al (1994) Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo. Biochim Biophys Acta 1195:181–184Google Scholar
  15. 15.
    Kamada H, Tsutsumi Y, Yamamoto Y et al (2000) Antitumor activity of tumor necrosis factor-a conjugated with polyvinylpyrrolidone on solid tumors in mice. Cancer Res 60:6416–6420Google Scholar
  16. 16.
    D’souza AJM, Schowen RL, Topp EM (2003) Polyvinylpyrrolidone-drug conjugate: synthesis and release mechanism. J Control Release 94:91–100Google Scholar
  17. 17.
    Luo L, Ranger M, Lessard DG et al (2004) Novel amphiphilic diblock copolymer of low molecular weight poly(N-vinylpyrrolidone)-block-poly(d,l-lactide): synthesis, characterization, and micellization. Macromolecules 37:4008–4013Google Scholar
  18. 18.
    Lele BS, Leroux JC (2002) Synthesis and micellar characterization of novel amphiphilic A-B-A triblock copolymers of N-(2-Hydroxypropyl) methacrylamide or N-Vinyl-2-pyrrolidone with poly(ε-caprolactone). Macromolecules 35:6714–6723Google Scholar
  19. 19.
    Yokoyama F, Masada I, Shimamura K et al (1986) Morphology and structure of highly elastic poly-(vinyl alcohol) hydrogel prepared by repeated freezing-and-melting. Colloid Polym Sci 264:559–561Google Scholar
  20. 20.
    Hassan CM, Stewart JE, Peppas NA (2000) Diffusional characteristics of freeze/thawed poly(vinyl alcohol) hydrogels: applications to protein controlled release from multilaminate devices. Eur J Pharm Biopharm 49:161–165Google Scholar
  21. 21.
    Mansur HS, Sadahira CM, Souza AN et al (2008) FT-IR spectroscopy characterization of poly (vinyl alcohol) hydrogel with different hydrolysis degree and chemically crosslinked with glutaraldehyde. Mater Sci Eng C 28(4):539–548Google Scholar
  22. 22.
    Lin HL, Liu YF, Yu TL et al (2005) Light scattering and viscoelasticity study of poly(vinyl alcohol)-borax aqueous solutions and gels. Polymer 46:5541–5549Google Scholar
  23. 23.
    Mühlebach A, Müller B, Pharisa C et al (1997) New water-soluble photo crosslinkable polymers based on modified poly(vinyl alcohol). J Polym Sci A Polym Chem 35(16):3603–3611Google Scholar
  24. 24.
    Peppas NA, Wright SL (1996) Solute diffusion in poly(vinyl alcohol)/poly(acrylic acid) interpenetrating networks. Macromolecules 29:8798–8804Google Scholar
  25. 25.
    Peppas NA, Wright SL (1998) Drug diffusion and binding in ionisable interpenetrating networks from poly(vinyl alcohol) and poly(acrylic acid). Eur J Pharm Biopharm 4:15–29Google Scholar
  26. 26.
    Juntanon K, Niamlang S, Rujiravanit R et al (2008) Electrically controlled release of sulfosalicylic acid from crosslinked poly(vinyl alcohol) hydrogel. Int J Pharm 356:1–11Google Scholar
  27. 27.
    Yu FT, Yu MD, Xian WH et al (2007) Rheological characterisation of a novel thermosensitive chitosan/poly(vinyl alcohol) blend hydrogel. Carbohydr Polym 67:491–499Google Scholar
  28. 28.
    Wu G, Suc B, Zhang W et al (2008) In vitro behaviors of hydroxyapatite reinforced poly(vinyl alcohol) hydrogel composite. Mater Chem Phys 107:364–369Google Scholar
  29. 29.
    Kim JO, Park JK, Kim JH et al (2004) Development of poly(vinyl alcohol)-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone. Polymer 45:7129–7136Google Scholar
  30. 30.
    Nishioa Y, Yamada A, Ezaki K et al (2004) Preparation and magnetometric characterization of iron oxide-containing alginate/poly(vinyl alcohol) networks. Polymer 45:7129–7136Google Scholar
  31. 31.
    Franssen O, van ooijen RD, de Boer D et al (1999) Enzymatic degradation of cross-linked dextrans. Macromolecules 32:2896–2902Google Scholar
  32. 32.
    Stenekes RJH, Loebis AE, Fernandes CM et al (2001) Degradable dextran microspheres for the controlled release of liposomes. Int J Pharm 214:17–20Google Scholar
  33. 33.
    van Dijk-Wolthuis WNE, Franssen O, Talsma H et al (1995) Synthesis, characterization and polymerization of glycidyl methacrylate derivatized dextran. Macromolecules 28:6317–6322Google Scholar
  34. 34.
    Massia SP, Stark J (2001) Immobilized RGD peptides on surface-grafted dextran promote biospecific cell attachment. J Biomed Mater Res 56(3):390–399Google Scholar
  35. 35.
    Rouzes C, Leonard M, Durand A et al (2003) Influence of polymeric surfactants on the properties of drug-loaded PLA nanospheres. Colloids Surf B 32:125–135Google Scholar
  36. 36.
    De Sousa DA, Leonard M, Dellacherie E (2001) Surface properties of polystyrene nanoparticles coated with dextrans and dextran-PEO Copolymers. Effect of polymer architecture on protein adsorption. Langmuir 17:4386–4391Google Scholar
  37. 37.
    De Sousa DA, Leonard M, Dellacherie E (2000) Surface modification of polystyrene nanoparticles using dextrans and dextran-POE copolymers: polymer adsorption and colloidal characterization. J Biomater Sci Polym Ed 11:1395–1410Google Scholar
  38. 38.
    Chen FM, Zhao YM, Sun HH et al (2007) Novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hydrogel scaffolds containing microspheres loaded with bone morphogenetic proteins: Formulation and characteristics. J Control Release 118:65–77Google Scholar
  39. 39.
    Mitra S, Gaur U, Ghosh PC et al (2001) Tumour targeted delivery of encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier. J Control Release 74:317–323Google Scholar
  40. 40.
    Barreiro-Iglesias R, Coronilla R, Concheiro A et al (2005) Preparation of chitosan beads by simultaneous cross-linking/insolubilisation in basic pH rheological optimisation and drug loading/release behaviour. Eur J Pharm Sci 24:77–84Google Scholar
  41. 41.
    Cho JH, Kim SH, Park KD et al (2004) Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer. Biomaterials 25:5743–5751Google Scholar
  42. 42.
    Chung HJ, Go DH, Ba JW et al (2005) Synthesis and characterization of Pluronic grafted chitosan copolymer as a novel injectable biomaterial. Curr Appl Phys 5:485–488Google Scholar
  43. 43.
    Dufes C, Schätzlein AG, Tetley L et al (2000) Niosomes and polymeric chitosan based vesicles bearing transferring and glucose ligands for drug targeting. Pharm Res 17:1250–1258Google Scholar
  44. 44.
    Hejazi R, Amiji M (2003) Chitosan-based gastrointestinal delivery systems. J Control Release 89:151–165Google Scholar
  45. 45.
    Ormrod DJ, Holmes CC, Miller TE (1998) Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis. Atherosclerosis 138:329–334Google Scholar
  46. 46.
    Gallaher CM, Munion J, Hesslink R Jr et al (2000) Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr 130:2753–2759Google Scholar
  47. 47.
    Chen AH, Liu SC, Chen CY et al (2008) Comparative adsorption of Cu(II), Zn(II), and Pb(II) ions in aqueous solution on the crosslinked chitosan with epichlorohydrin. J Hazard Mater 154(1–3):184–191Google Scholar
  48. 48.
    Chen F, Zhang ZR, Yuan F et al (2008) In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery. Int J Pharm 349:226–233Google Scholar
  49. 49.
    Grant GT, Morris ER, Rees DA et al (1973) Biological interactions between polysaccharides and divalent cations: the egg-box model. FEBS Lett 32(1):195–198Google Scholar
  50. 50.
    Morris ER (1974) Molecular interactions in polysaccharide gelation. Br Polym J 18:14–21Google Scholar
  51. 51.
    Smidsrod O (1974) Molecular basis for some physical properties of alginates in gel state. Faraday Discuss Chem Soc 57:263–274Google Scholar
  52. 52.
    Ouwerx C, Velings N, Mestdagh MM et al (1998) Physico-chemical properties and rheology of alginate gel beads formed with various divalent cations. Polym Gels Netw 6:393–408Google Scholar
  53. 53.
    Montero P, Pérez-Mateos M (2002) Effects of Na+, K+ and Ca2+ on gels formed from fish mince containing a carrageenan or alginate. Food Hydrocol 16:375–385Google Scholar
  54. 54.
    Murata Y, Hirai D, Kofuji KE (2004) Properties of an alginate gel bead containing a chitosan-drug salt. Biol Pharm Bull 27:440–442Google Scholar
  55. 55.
    Murata Y, Jinno D, Kofuji K et al (2004) Properties of calcium-induced gel beads prepared with alginate and hydrolysates. Chem Pharm Bull 52:605–607Google Scholar
  56. 56.
    Liu X, Xu W, Liu Q et al (2004) Swelling behaviour of alginate–chitosan microcapsules prepared by external gelation or internal gelation technology. Carbohydr Polym 56:459–464Google Scholar
  57. 57.
    Lin YH, Liang HF, Chung CK et al (2005) Physical crosslinked alginate/N, O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials 26:2105–2113Google Scholar
  58. 58.
    Holte Ø, Onsøyen E, Myrvold R et al (2003) Sustained release of water-soluble drug from directly compressed alginate tablets. Eur J Pharm Sci 20:403–407Google Scholar
  59. 59.
    Bajpai SK, Shubhra S (2004) Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions. React Funct Polym 59:129–140Google Scholar
  60. 60.
    Denis D, van Mathieu S, Rose MG et al (2006) The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats. Biomaterials 27:3201–3208Google Scholar
  61. 61.
    Choi YH, Lee JH, Yuk SH (2006) Core/shell macrobeads for the protection of islets from immune system rejection. J Bioact Compat Polym 21:71–81Google Scholar
  62. 62.
    Koch S, Schwinger C, Kressler J et al (2003) Alginate encapsulation of genetically engineered mammalian cells: comparison of production devices, methods and microcapsule characteristics. J Microencapsul 20:303–316Google Scholar
  63. 63.
    Xiong XY, Tam KC, Gan LH (2006) Polymeric nanostructures for drug delivery applications based on pluronic copolymer systems. J Nanosci Nanotechnol 6(9–10):2638–2650Google Scholar
  64. 64.
    Alexandridis P, Hatton TA (1995) Poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling. Colloids Surf A Physicochem Eng Asp 96:1–46Google Scholar
  65. 65.
    Ruel-Gariepy E, Leroux JC (2004) In situ-forming hydrogels-review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426Google Scholar
  66. 66.
    Dumortier G, Grossiord JL, Agnely F et al (2006) A review of Poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res 23:2709–2728Google Scholar
  67. 67.
    Newa M, Bhandari KH, Li DX (2007) Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int J Pharm 343(1–2):228–237Google Scholar
  68. 68.
    Yong CS, Oh YK, Kim YI et al (2005) Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats. Int J Pharm 301(1–2):54–61Google Scholar
  69. 69.
    Kayes JB, Rawlins DA (1979) Adsorption characteristics of certain poloexyethylene polyoxypropylene block co-polymers on polysterene latex. Colloid Polym Sci 257:622–629Google Scholar
  70. 70.
    Li JT, Caldwell KD, Rapoport N (1994) Surface properties of pluronic-coated polymeric colloids. Langmuir 10:4475–4482Google Scholar
  71. 71.
    Illum L, Jacobsen LO, Muller RH et al (1987) Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages. Biomaterials 8:113–117Google Scholar
  72. 72.
    Tan JS, Butterfield DE, Voycheck CL et al (1993) Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats. Biomaterials 14:823–833Google Scholar
  73. 73.
    Stolnik S, Dunn SE, Garnett MC et al (1994) Surface modification of poly(lactide-co-glycolide) nanoparticles by biodegradable poly(lactide)-poly(ethylene glycol) copolymer. Pharm Res 11:1800–1808Google Scholar
  74. 74.
    Bazile D, Prud’homme C, Bassoullet MT et al (1995) Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocyte system. J Pharm Sci 84:493–498Google Scholar
  75. 75.
    Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymer. J Control Release 63:155–163Google Scholar
  76. 76.
    Jeong B, Bae YH, Kim SW (1999) Thermoreversible gelation of PEG–PLGA–PEG triblock copolymer aqueous solutions. Macromolecules 32:7064–7069Google Scholar
  77. 77.
    Lee DS, Shim MS, Kim SW et al (2001) Novel thermoreversible gelation of biodegradable PLGA-block–PEO-block–PLGA triblock copolymers in aqueous solution. Macromol Rapid Commun 22:587–592Google Scholar
  78. 78.
    Jeong B, Bae YH, Kim SW (2000) In situ gelation of PEG–PLGA–PEG triblock copolymer aqueous solutions and degradation thereof. J Biomed Mater Res 50:171–177Google Scholar
  79. 79.
    Kim SC, Kim DW, Shim YH et al (2001) In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release 72:191–202Google Scholar
  80. 80.
    Kim T, Kim D, Chung J (2004) Phase I and pharmacokinetic study of genexol-PM, a cremophor-free, polymeric micelleformulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res 10:3708–3716Google Scholar
  81. 81.
    Heskins M, Guillet JJ (1968) Solution properties of poly(N-isopropylacrylamide). J Macromol Sci Part A Pure Appl Chem 2(8):1441–1455Google Scholar
  82. 82.
    Xu J, Ye J, Liu S (2007) Synthesis of well-defined cyclic poly(N-isopropylacrylamide) via click chemistry and its unique thermal phase transition behavior. Macromolecules 40(25):9103–9110Google Scholar
  83. 83.
    Feil H, Bae YH, Feijen J et al (1993) Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules 26(10):2496–2500Google Scholar
  84. 84.
    Zhang J, Pelton R, Deng Y (1995) Temperature-dependent contact angles of water on poly(N-isopropylacrylamide) gels. Langmuir 11(6):2301–2302Google Scholar
  85. 85.
    Maeda T, Kanda T, Yonekura Y et al (2006) Hydroxylated poly(N-isopropylacrylamide) as functional thermoresponsive materials. Biomacromolecules 7(2):545–549Google Scholar
  86. 86.
    Canavan HE, Cheng X, Graham DJ et al (2005) Surface characterization of the extracellular matrix remaining after cell detachment from a thermoresponsive polymer. Langmuir 21:1949–1955Google Scholar
  87. 87.
    Yoshida R, Uchida K, Kaneko Y et al (1995) Comb-type grafted hydrogels with rapid de-swelling response to temperature changes. Nature 374:240–242Google Scholar
  88. 88.
    Tuncel A, Ozdemir A (2000) Thermally reversible VPBA–NIPAM copolymer gels for nucleotide adsorption.J Biomater Sci Polym Ed 11:817–831Google Scholar
  89. 89.
    Lin HH, Cheng YL (2001) In-situ thermoreversible gelation of block and star copolymers of Poly(ethylene glycol) and Poly(N-isopropylacrylamide) of varying architectures. Macromolecules 34:3710–3715Google Scholar
  90. 90.
    Kwon OH, Kikuchi A, Yamato M et al (2000) Rapid cell sheet detachment from Poly(N-isopropylacrylamide)-grafted porous cell culture membranes. J Biomed Mater Res 50:82–89Google Scholar
  91. 91.
    Yamato M, Kwon OH, Hirose M et al (2000) Novel patterned cell coculture utilizing thermally responsive grafted polymer surfaces. J Biomed Mater Res 55:137–140Google Scholar
  92. 92.
    Shimizu T, Yamato M, Kikuchi A et al (2001) Two-dimensional manipulation of cardiac myocyte sheets utilizing temperature-responsive culture dishesauguments the pulsatile amplitude. Tissue Eng 7:141–151Google Scholar
  93. 93.
    Li C, Buurma NJ, Haq I et al (2005) Synthesis and characterization of biocompatible, thermoresponsive ABC and ABA triblock copolymer gelators. Langmuir 21(24):11026–11033Google Scholar
  94. 94.
    Hay DNT, Rickert PG, Seifert S et al (2004) Thermoresponsive nanostructures by self-assembly of a poly(N-isopropylacrylamide)-lipid conjugate. J Am Chem Soc 126(8):2290–2291Google Scholar
  95. 95.
    Jeong B, Choi YK, Bae YH et al (1999) New biodegradable polymers for injectable drug delivery systems. J Control Release 62:109–114Google Scholar
  96. 96.
    Lee SB, Park EK, Lim YM et al (2006) Preparation of alginate/poly(N-isopropylacrylamide) semi-interpenetrating and fully interpenetrating polymer network hydrogels with γ-ray irradiation and their swelling behaviors. J Appl Pol Sci 100:4439–4446Google Scholar
  97. 97.
    Kim MH, Kim JC, Lee HY et al (2005) Release property of temperature-sensitive alginate beads containing poly(N-isopropylacrylamide). Colloids Surf B Biointerfaces 46:57–61Google Scholar
  98. 98.
    Neradovic D, Soga O, van Nostrum CF et al (2004) The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups. Biomaterials 25:2409–2418Google Scholar
  99. 99.
    Wei H, Zhang XZ, Zhou Y et al (2006) Selfassembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methyl methacrylate). Biomaterials 27:2028–2034Google Scholar
  100. 100.
    Kreibig U, Vollmer M (1996) Optical properties of metal clusters. Springer verlag, BerlinGoogle Scholar
  101. 101.
    Turkevich J, Stevenson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55Google Scholar
  102. 102.
    Shukla R, Bansal V, Chaudhary M et al (2005) Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir 21:10644–10654Google Scholar
  103. 103.
    Connor EE, Mwamuka J, Gole A et al (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327Google Scholar
  104. 104.
    Kim DK, Park SJ, Lee JH et al (2007) Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. J Am Chem Soc 129:7661–7665Google Scholar
  105. 105.
    Raynal I, Prigent P, Peyramaure S et al (2004) Macrophage endocytosis of superparamagnetic iron oxide nanoparticles mechanisms and comparison of ferumoxides and ferumoxtran-10. Invest Radiol 39:56–63Google Scholar
  106. 106.
    Rogers WJ, Basu P (2005) Factors regulating macrophage endocytosis of nanoparticles: implications for targeted magnetic resonance plaque imaging. Atherosclerosis 178:67–73Google Scholar
  107. 107.
    Woodle MC, Engbers CM, Zalipsky S (1994) New amphipatic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes. Bioconjug Chem 5:493–496Google Scholar
  108. 108.
    Fong YC, Chia HS, Yu SY (2005) Characterization of aqueous dispersions of Fe3O4 nanoparticles and their biomedical applications. Biomaterials 26:729–738Google Scholar
  109. 109.
    Knag YS, Risbud S, Rabolt JF et al (1996) Synthesis and characterizations of nanometer-size Fe3O4 and Fe2O3 particles. Chem Mater 8:2209–2211Google Scholar
  110. 110.
    Mann S, Hannington JP (1988) Formation of iron oxides in unilamellar vesicles. J Colloid Interface Sci 122:326–335Google Scholar
  111. 111.
    Domingo C, Rodriguez Clemente R, Blesa MA (1993) Kinetics of oxidative precipitation of iron oxide particles. Colloids Surf A 79:177–189Google Scholar
  112. 112.
    Euliss LE, Grancharov SG, O’Brien S et al (2003) Cooperative assembly of magnetic nanoparticles and block copolypeptides in aqueous media. Nano Lett 3:1489–1493Google Scholar
  113. 113.
    Park J, An K, Hwang Y et al (2004) Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater 3:891–895Google Scholar
  114. 114.
    Swadeshmukul S, Rovelyn T, Nikoleta T et al (2001) Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: the effect of nonionic surfactants. Langmuir 17:2900–2906Google Scholar
  115. 115.
    Li L, Choo ESG, Yi JB et al (2008) Superparamagnetic silica composite nanospheres (SSCNs) with ultrahigh loading of iron oxide nanoparticles via an oil-in-DEG microemulsion route. Chem Mater 20:6292–6294Google Scholar
  116. 116.
    Jolivet JP, Belleville P, Tronc E et al (1992) Influence of Fe(II) on the formation of the spinel iron oxide in alkaline medium. Clays Clay Miner 40:531–539Google Scholar
  117. 117.
    Cuyper MD, Joniau M (1988) Magnetoliposomes. Eur Biophys J 15:311–319Google Scholar
  118. 118.
    Massart R (1981) Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans Magn 17:1247–1248Google Scholar
  119. 119.
    Shah PS, Holmes JD, Johnston KP et al (2002) Size-selective dispersion of dodecanethiol-coated nanocrystals in liquid and supercritical ethane by density tuning. J Phys Chem B 106:2545–2551Google Scholar
  120. 120.
    Kitchens C, McLeod MC, Roberts B (2003) Solvent effects on the growth and steric stabilization of copper metallic nanoparticles in AOT reverse micelle systems. J Phys Chem B 107:11331–11338Google Scholar
  121. 121.
    Summers M, Eastoe J, Davis S (2002) Formation of BaSO4 nanoparticles in microemulsions with polymerized surfactant shells. Langmuir 18:5023–5026Google Scholar
  122. 122.
    Marchand KE, Tarret M, Lechaire JP et al (2003) Investigation of AOT-based microemulsions for the controlled synthesis of MoSx nanoparticles: an electron microscopy study. Colloids Surf A Physicochem Eng Asp 214:239–248Google Scholar
  123. 123.
    Husein M, Rodil E, Vera J (2003) Formation of silver chloride nanoparticles in microemulsions by direct precipitation with the surfactant counterion. Langmuir 19:8467–8474Google Scholar
  124. 124.
    Charinpanitkul T, Chanagul A, Dutta J et al (2005) Effects of cosurfactant on ZnS nanoparticle synthesis in microemulsion. Sci Technol Adv Mater 6:266–271Google Scholar
  125. 125.
    Pileni MP (2003) The role of soft colloidal templates in controlling the size and shape of inorganic nanocrystals. Nat Mater 2:145–150Google Scholar
  126. 126.
    Singh R, Kumar S (2006) Effect of mixing on nanoparticle formation in micellar route. Chem Eng Sci 61:192–204Google Scholar
  127. 127.
    Wang YX, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11:2319–2331Google Scholar
  128. 128.
    Stark DD, Weissleder R, Elizondo G et al (1988) Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver. Radiology 168:297–301Google Scholar
  129. 129.
    Hamm B, Staks T, Taupitz M et al (1994) Contrast-enhanced MR imaging of liver and spleen: first experience in humans with a new superparamagnetic iron oxide. J Magn Reson Imag 4:659–668Google Scholar
  130. 130.
    Weissleder R, Bogdanov A, Neuwelt EA (1995) Long-circulating iron oxides for MR imaging. Adv Drug Deliv Rev 16:321–334Google Scholar
  131. 131.
    Wilson SR, Burnes PN, Muradali D et al (2000) Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis. Radiology 215:153–161Google Scholar
  132. 132.
    Kedar RP, Cosgrove D, McCready VR et al (1996) Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress. Radiology 198:679–686Google Scholar
  133. 133.
    Halpern EJ, Rosenberg M, Gomella LG (2001) Prostate cancer: contrast-enhanced US for detection. Radiology 219:219–225Google Scholar
  134. 134.
    Ellegala DB, Leong-Poi H, Carpenter JE et al (2003) Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation 108:336–341Google Scholar
  135. 135.
    Leong-Poi H, Christiansen J, Klibanov AL et al (2003) Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 107:455–460Google Scholar
  136. 136.
    Weller GER, Wong MKK, Modzelewski RA et al (2005) Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine–arginine–leucine. Cancer Res 65:533–539Google Scholar
  137. 137.
    Stieger SM, Dayton PA, Borden MA et al (2007) Imaging of angiogenesis using cadence contrast pulse sequencing and targeted contrast agents. Contrast Media Mol Imaging 3(1):9–18Google Scholar
  138. 138.
    Unger E, Metzger P, Krupinski E et al (2000) The use of a thrombus-specific ultrasound contrast agent to detect thrombus in arteriovenous fistulae. Invest Radiol 35:86–89Google Scholar
  139. 139.
    Lindner JR, Song J, Christiansen J et al (2001) Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation 104:2107–2112Google Scholar
  140. 140.
    Linker RA, Reinhardt M, Bendszus M et al (2005) In vivo molecular imaging of adhesion molecules in experimental autoimmune encephalomyelitis (EAE). J Autoimmun 25:199–205Google Scholar
  141. 141.
    Takalkar AM, Klibanov AL, Rychak JJ et al (2004) Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J Control Release 96:473–482Google Scholar
  142. 142.
    Rychak JJ, Li B, Acton ST et al (2006) Selectin ligands promote ultrasound contrast agent adhesion under shear flow. Mol Pharmacol 3:516–524Google Scholar
  143. 143.
    Lankford M, Behm CZ, Yeh J et al (2006) Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging. Invest Radiol 41(10):721–728Google Scholar
  144. 144.
    Rychak JJ, Lindner JR, Ley K et al (2006) Deformable gas-filled microbubbles targeted to P-selectin. J Control Release 114(3):288–299Google Scholar
  145. 145.
    Klibanov AL (2005) Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. Bioconjug Chem 16:9–17Google Scholar
  146. 146.
    Rychak JJ, Klibanov AL, Ley KF et al (2007) Enhanced targeting of ultrasound contrast agents using acoustic radiation force. Ultrasound Med Biol 33(7):1132–1139Google Scholar
  147. 147.
    Bakalova R, Zhelev Z, Ohba H et al (2005) Quantum dot-based western blot technology for ultrasensitive detection of tracer proteins. J Am Chem Soc 127(26):9328–9329Google Scholar
  148. 148.
    Zhelev Z, Bakalova R, Ohba H (2006) Uncoated, broad fluorescent, and size-homogeneous CdSe quantum dots for bioanalyses. Anal Chem 78(1):321–330Google Scholar
  149. 149.
    Mingyong H, Xiaohu G, Jack ZS (2001) Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 19:631–635Google Scholar
  150. 150.
    Bruchez M Jr, Moronne M, Gin P (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016Google Scholar
  151. 151.
    Han M, Gao X, Su JZ (2001) Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 19:631–635Google Scholar
  152. 152.
    Chan WC, Nie S (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018Google Scholar
  153. 153.
    Chen Y, Rosenzweig Z (2002) Luminescent CdSe quantum dot doped stabilized micelles. Nano lett 2(11):1299–1302Google Scholar
  154. 154.
    Kirchner C, Liedl T, Kudera S et al (2005) Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. Nano Lett 5:331–338Google Scholar
  155. 155.
    O’Brien P, Cummins SS, Darcy D et al (2003) Quantum dot-labelled polymer beads by suspension polymerization. Chem Commun 3:2532–2533Google Scholar
  156. 156.
    Rabin O, Manuel Perez J, Grimm J (2006) An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater 5(2):118–122Google Scholar
  157. 157.
    Hainfeld JF, Slatkin DN, Focella TM (2006) Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 79(939):248–253Google Scholar
  158. 158.
    Lee HR, Lee EH, Kim DK et al (2006) Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. J Am Chem Soc 128:7383–7389Google Scholar
  159. 159.
    Kim DK, Park SJ, Lee JH et al (2007) Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. J Am Chem Soc 29:7661–7665Google Scholar
  160. 160.
    Huang H, Yang X (2003) Chitosan mediated assembly of gold nanoparticles multilayer. Colloids Surf A Physicochem Eng Asp 226(1–3):77–86Google Scholar
  161. 161.
    Aqil A, Qiu H, Greisch JF et al (2008) Coating of gold nanoparticles by thermosensitive poly(N-isopropylacrylamide) end-capped by biotin. Polymer 49:1145–1153Google Scholar
  162. 162.
    Lee HY, Lee SH, Xu C et al (2008) Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent. Nanotechnology 19:165101–165107Google Scholar
  163. 163.
    Jain TK, Morales MA, Sahoo SK et al (2005) Iron oxide nanoparticles for sustained delivery of anticancer agents. Mol Pharm 2(3):194–205Google Scholar
  164. 164.
    Dutza S, Andrä W, Hergta R et al (2007) Influence of dextran coating on the magnetic behaviour of iron oxide nanoparticles. J Magn Magn Mater 311:51–54Google Scholar
  165. 165.
    Kim EH, Ahn YK, Lee HS (2007) Biomedical applications of superparamagnetic iron oxide nanoparticles encapsulated within chitosan. J Alloys Compd 434–435:633–636Google Scholar
  166. 166.
    Patel D, Moon JY, Chang YM et al (2008) Poly(d,l-lactide-co-glycolide) coated superparamagnetic iron oxide nanoparticles: synthesis, characterization and in vivo study as MRI contrast agent. Colloids Surf A Physicochem Eng Asp 313–314:91–94Google Scholar
  167. 167.
    Yang X, Chen Y, Yuan R et al (2008) Folate-encoded and Fe3O4-loaded polymeric micelles for dual targeting of cancer cells. Polymer 49:3477–3485Google Scholar
  168. 168.
    Li GY, Jiang YR, Huang KL et al (2008) Preparation and properties of magnetic Fe3O4-chitosan nanoparticles. J Alloys Compd 466(1–2):451–456Google Scholar
  169. 169.
    Conroy S, Raymond S, Miqin Z (2006) Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J Biomed Mater Res 78A:550–570Google Scholar
  170. 170.
    Peer D, Karp JM, Hong SP et al (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760Google Scholar
  171. 171.
    Norased N, Erik B, Jimin R (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6(11):2427–2430Google Scholar
  172. 172.
    von zur Muhlena C, von Elverfeldt D, Bassler N et al (2007) Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging of atherosclerotic plaques. Atherosclerosis 193:102–111Google Scholar
  173. 173.
    Derfus AM, Chan WCW, Bhatia SN (2004) Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11–18Google Scholar
  174. 174.
    Hardman RA (2006) Toxicological review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172Google Scholar
  175. 175.
    Guo G, Liu W, Liang J et al (2006) Preparation and characterization of novel CdSe quantum dots modified with poly(d,l-lactide) nanoparticles. Mater Lett 60:2565–2568Google Scholar
  176. 176.
    Zhang H, Wang C, Li M et al (2005) Fluorescent nanocrystal–polymer composites from aqueous nanocrystals: methods without ligand exchange. Chem Mater 17:4783–4788Google Scholar
  177. 177.
    Zhang H, Wang C, Li M et al (2005) Fluorescent nanocrystal–polymer complexes with flexible processability. Adv Mater 17:853–857Google Scholar
  178. 178.
    Gong Y, Gao M, Wang D et al (2005) Incorporating fluorescent CdTe nanocrystals into a hydrogel via hydrogen bonding: toward fluorescent microspheres with temperature-responsive properties. Chem Mater 17:2648–2653Google Scholar
  179. 179.
    Yang X, Zhang Y (2004) Encapsulation of quantum nanodots in polystyrene and silica micro-/nanoparticles. Langmuir 20:6071–6073Google Scholar
  180. 180.
    Mokari T, Sertchook H, Aharoni A et al (2005) Nano@micro: general method for entrapment of nanocrystals in sol–gel-derived composite hydrophobic silica spheres. Chem Mater 17:258–263Google Scholar
  181. 181.
    Watanabe TM, Higuchi H (2007) Stepwise movements in vesicle transport of HER2 by motor proteins in living cells. Biophys J 92:4109–4120Google Scholar
  182. 182.
    Bruchez MP (2005) Turning all the lights on: quantum dots in cellular assays. Curr Opin Chem Biol 9(5):533–537Google Scholar
  183. 183.
    Tartis MS, McCallan J, Lum AF et al (2006) Therapeutic effects of paclitaxel-containing ultrasound contrast agents. Ultrasound Med Biol 32(11):1771–1780Google Scholar
  184. 184.
    Chen SY, Ding JH, Bekeredjian R et al (2006) Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology. Proc Natl Acad Sci U S A 103(22):8469–8474Google Scholar
  185. 185.
    Kimmel E (2006) Cavitation bioeffects. Crit Rev Biomed Eng 34(2):105–161Google Scholar
  186. 186.
    Kipshidze NN, Porter TR, Dangas G et al (2005) Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model. Catheter Cardiovasc Interv 64(3):389–394Google Scholar
  187. 187.
    Korpanty G, Chen S, Shohet RV et al (2005) Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles. Gene Ther 12(17):1305–1312Google Scholar
  188. 188.
    Unger EC, Hersh E, Vannan M et al (2001) Local drug and gene delivery through microbubbles. Prog Cardiovasc Dis 44(1):45–54Google Scholar
  189. 189.
    Kheirolomoom A, Dayton PA, Lum AFH et al (2007) Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle. J Control Release 118(3):275–284Google Scholar
  190. 190.
    Lee LY, Wang CH, Smith KA (2008) Supercritical antisolvent production of biodegradable micro- and nanoparticles for controlled delivery of paclitaxel. J Control Release 125:96–106Google Scholar
  191. 191.
    Suzaki R, Takizawa T, Negishi Y et al (2008) Tumor specific ultrasound enhanced gene transfer in vivo with novel liposomal bubbles. J Control Release 125:137–144Google Scholar
  192. 192.
    Leong-Poi H, Song J, Rim SJ et al (2002) Influence of microbubble shell properties on ultrasound signal: implications for low-power perfusion imaging. J Am Soc Echocardiogr 15(10):1269–1276Google Scholar
  193. 193.
    Brannigan M, Burns PN, Wilson SR (2004) Blood flow patterns in focal liver lesions at microbubble-enhanced US. Radiographics 24(4):921–935Google Scholar
  194. 194.
    Toublan FJJ, Boppart SA, Suslick KS (2006) Tumor targeting by surface-modified protein microspheres. J Am Chem Soc 128:3472–3473Google Scholar
  195. 195.
    Oh KS, Kim RS, Yuk SH et al (2008) Gold/chitosan/pluronic composite nanoparticles for drug delivery. J Appl Polym Sci 108:3239–3244Google Scholar
  196. 196.
    Nasongkla N, Bey E, Ren J et al (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6(11):2427–2430Google Scholar
  197. 197.
    Ungar EC, Porter T, Culp W et al (2004) Therapeutic applications of lipid-coated microbubbles. Adv Drug Deliv Rev 56:1291–1314Google Scholar
  198. 198.
    Lum AFH, Borden MA, Dayton PA et al (2006) Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles. J Control Release 111:128–134Google Scholar
  199. 199.
    Shortencarier MJ, Dayton PA, Bloch SH et al (2004) A method for radiation-force localized drug delivery using gas-filled lipospheres. IEEE Trans Ultrason Ferroelectr Freq Control 51(7):822–831Google Scholar
  200. 200.
    Rapoport N, Gao Z, Kennedy A (2007) Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. J Natl Cancer Inst 99(14):1095–1106Google Scholar
  201. 201.
    Gao Z, Fain H, Rapoport N (2005) Controlled and targeted tumor chemotherapy by micellar-encapsulated drug and ultrasound. J Control Release 102:203–221Google Scholar
  202. 202.
    Brad PB, Aravind A, Parag V et al (2007) Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med. doi:10.1038/nm1581Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Advanced MaterialsHannam UniversityDaejeonKorea

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