Pharmaceutical Micelles: Combining Longevity, Stability, and Stimuli Sensitivity

  • Myrra G. Carstens
  • Cristianne J. F. Rijcken
  • Cornelus F. van Nostrum
  • Wim E. Hennink
Part of the Fundamental Biomedical Technologies book series (FBMT, volume 4)

The primary focus of this chapter is the description and discussion of longevity and stability of drug-loaded polymeric micelles after intravenous injection, and the possibility to release their payload in a controlled manner upon local and/or external stimuli.


Cloud Point Block Copolymer Critical Micelle Concentration Diblock Copolymer Polymeric Micelle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abra, R. M., Bosworth, M. E., and Hunt, C. A. 1980. Liposome disposition in vivo: effects of predosing with lipsomes. Res. Commun. Chem. Pathol. Pharmacol. 29: 349–360.PubMedGoogle Scholar
  2. Adams, M. L., Lavasanifar, A., and Kwon, G. S. 2003. Amphiphilic block copolymers for drug delivery. J. Pharm. Sci. 92: 1343–1355.PubMedGoogle Scholar
  3. Ai, H., et al. 2005. Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv. Mater. 17: 1949–1952.Google Scholar
  4. Akagi, T., et al. 2006. Hydrolytic and enzymatic degradation of nanoparticles based on amphiphilic poly(gamma-glutamic acid)-graft-L-phenylalanine copolymers. Biomacromolecules 7: 297–303.PubMedGoogle Scholar
  5. Allen, T. M. and Hansen, C. 1991. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim. Biophys. Acta 1068: 133–141.PubMedGoogle Scholar
  6. Allen, C., Maysinger, D., and Eisenberg, A. 1999. Nano-engineering block copolymer aggregates for drug delivery. Colloid Surf B 16: 3–27.Google Scholar
  7. Allen, C., et al. 2000. Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone. J. Control. Release 63: 275–286.PubMedGoogle Scholar
  8. Anton, P., Heinze, J., and Laschewsky, A. 1993. Redox-active monomeric and polymeric surfactants. Langmuir 9: 77–85.Google Scholar
  9. Attwood, D. and Florence, A. T. 1983. In: Surfactant Systems: Their Chemistry, Pharmacy and Biology, p. 108–111. London: Chapman and Hall Ltd.Google Scholar
  10. Avgoustakis, K., et al. 2002. PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties. J. Control. Release 79: 123–135.PubMedGoogle Scholar
  11. Bae, Y., et al. 2003. Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsible to intracellular pH change. Angew. Chem. Int. Ed. Engl. 42: 4640–4643.PubMedGoogle Scholar
  12. Bae, Y., et al. 2005. Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjug. Chem. 16: 122–130.PubMedGoogle Scholar
  13. Bae, K. H., et al. 2006. Thermosensitive pluronic micelles stabilized by shell cross-linking with gold particles. Langmuir 22: 6380–6384.PubMedGoogle Scholar
  14. Barratt, G. M. 2000. Therapeutic applications of colloidal drug carriers. Pharm. Sci. Technol. Today 3: 163–171.PubMedGoogle Scholar
  15. Benahmed, A., Ranger, M., and Leroux, J. C. 2001. Novel polymeric micelles based on the amphiphilic diblock copolymer poly(N-vinyl-2-pyrrolidone)-block-poly(D, L-lactide). Pharm. Res. 18: 323–328.PubMedGoogle Scholar
  16. Besheer, A., et al. 2007. Hydrophobically modified hydroxyethyl starch: synthesis, characterization, and aqueous self-assembly into nano-sized polymeric micelles and vesicles. Biomacromolecules 8: 359–367.PubMedGoogle Scholar
  17. Bontha, S., Kabanov, A. V., and Bronich, T. K. 2006. Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs. J. Control. Release 114: 163–174.PubMedGoogle Scholar
  18. Bougard, F., et al. 2007. Synthesis and supramolecular organization of amphiphilic diblock copolymers combining poly(N, N-dimethylamino-2-ethyl methacrylate) and poly(ε-caprolactone). Langmuir 23: 2339–2345.PubMedGoogle Scholar
  19. Bronich, T. K., et al. 2005. Polymer micelle with cross-linked ionic core. J. Am. Chem. Soc. 127: 8236–8237.PubMedGoogle Scholar
  20. Butun, V., Billingham, N. C., and Armes, S. P. 1998. Unusual aggregation behavior of a novel tertiary amine methacrylate-based diblock copolymer: formation of micelles and reverse micelles in aqueous solution. J. Am. Chem. Soc. 120: 11818–11819.Google Scholar
  21. Butun, V., et al. 2006. A brief review of ‘schizophrenic’ block copolymers. React. Funct. Polym. 66: 157–165.Google Scholar
  22. Carstens, M. G., et al. 2006. Observations on the disappearance of the stealth property of PEGylated liposomes. Effects of lipid dose and dosing frequency. In: Liposome Technology, ed. G. Gregoriadis, London: CRC press.Google Scholar
  23. Carstens, M. G., et al. 2007a. Small oligomeric micelles based on end group modified mPEG-oligocaprolactone with monodisperse hydrophobic blocks. Macromolecules 40: 116–122.ADSGoogle Scholar
  24. Carstens, M. G., van Nosrum C. F., Verrijk R., de Leede L. G. J., Crommelin D. J. A., and Hennink W. E. 2008. A mechanistic study of the chemical and enzymatic degradation of PEG-oligo(e-caprolactone) micelles. J. Pharm. Sci. 97: 506–518.PubMedGoogle Scholar
  25. Cavallaro, G., et al. 2003. Poly(hydroxyethylaspartamide) derivatives as colloidal drug carrier systems. J. Control. Release 89: 285–295.PubMedGoogle Scholar
  26. Chen, C., et al. 2006. Biodegradable nanoparticles of amphiphilic triblock copolymers based on poly(3-hydroxybutyrate) and poly(ethylene glycol) as drug carriers. Biomaterials 27: 4804–4814.PubMedGoogle Scholar
  27. Cheng, J., et al. 2007. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 28: 869–876.PubMedGoogle Scholar
  28. Chilkoti, A., et al. 2002. Targeted drug delivery by thermally responsive polymers. Adv. Drug Deliv. Rev. 54: 613–630.PubMedGoogle Scholar
  29. Chung, T. W., et al. 2004. Novel micelle-forming block copolymer composed of poly(e-caprolactone) and poly(vinyl pyrrolidone). Polymer 45: 1591–1597.Google Scholar
  30. Cinteza, L. O., et al. 2006. Diacyllipid micelle-based nanocarrier for magnetically guided delivery of drugs in photodynamic therapy. Mol. Pharm. 3: 415–423.PubMedGoogle Scholar
  31. Cohen Stuart, M. A., et al. 2005. Assembly of polyelectrolyte-containing block copolymers in aqueous media. Curr. Opin. Colloid Interface Sci. 10: 30–36.Google Scholar
  32. Crommelin, D. J. A., Scherphof, G., and Storm, G. 1995. Active targeting with particulate carrier systems in the blood compartment. Adv. Drug Deliv. Rev. 17: 49–60.Google Scholar
  33. Cui, Z., Lee, B. H., and Vernon, B. L. 2007. New hydrolysis-dependent thermosensitive polymer for an injectable degradable system. Biomacromolecules 8: 1280–1286.PubMedGoogle Scholar
  34. Dams, E. T., et al. 2000. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J. Pharmacol. Exp. Ther. 292: 1071–1079.PubMedGoogle Scholar
  35. de Jong, S. J., et al. 2001. New insights into the hydrolytic degradation of poly(lactic acid): participation of the alcohol terminus. Polymer 42: 2795–2802.Google Scholar
  36. Desponds, A. and Freitag, R. 2003. Synthesis and characterization of photoresponsive N-isopropylacrylamide cotelomers. Langmuir 19: 6261–6270.Google Scholar
  37. Djordjevic, J., Barch, M., and Uhrich, K. E. 2005. Polymeric micelles based on amphiphilic scorpion-like macromolecules: novel carriers for water-insoluble drugs. Pharm. Res. 22: 24–32.PubMedGoogle Scholar
  38. Dong, Y. and Feng, S. 2004. Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 25: 2843–2849.PubMedGoogle Scholar
  39. Dubertret, B., et al. 2002. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298: 1759–1762.PubMedADSGoogle Scholar
  40. Engin, K., et al. 1995. Extracellular pH distribution in human tumours. Int. J. Hyperthermia 11: 211–216.PubMedGoogle Scholar
  41. Fang, C., et al. 2006. In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: effect of MePEG molecular weight and particle size. Eur. J. Pharm. Sci. 27: 27–36.PubMedGoogle Scholar
  42. Feil, H., et al. 1993. Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules 26: 2496–2500.ADSGoogle Scholar
  43. Forrest, M. L., et al. 2006. Lipophilic prodrugs of Hsp90 inhibitor geldanamycin for nanoencapsulation in poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles. J. Control. Release 116: 139–149.PubMedGoogle Scholar
  44. Gan, Z., et al. 1999. Enzymatic biodegradation of poly(ethylene oxide-G-caprolactone) diblock copolymer and its potential biomedical applications. Macromolecules 32: 590–594.ADSGoogle Scholar
  45. Gao, Z., et al. 2003. PEG-PE/phosphatidylcholine mixed immunomicelles specifically deliver encapsulated taxol to tumor cells of different origin and promote their efficient killing. J. Drug Target. 11: 87–92.PubMedGoogle Scholar
  46. Gao, X., et al. 2004. In vivo cancer targeting and imaging with semiconductor quantum dots. Nature 22: 969–976.Google Scholar
  47. Gao, Z. -G., Fain, H. D., and Rapoport, N. 2005. Controlled and targeted tumor chemotherapy by micellar-encapsulated drug and ultrasound. J. Control. Release 102: 203–222.PubMedGoogle Scholar
  48. Gaucher, G., et al. 2005. Block copolymer micelles: preparation, characterization and application in drug delivery. J. Control. Release 109: 169–188.PubMedGoogle Scholar
  49. Geng, Y. and Discher, D. E. 2005. Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles. J. Am. Chem. Soc. 127: 12780–12781.PubMedGoogle Scholar
  50. Geng, Y. and Discher, D. E. 2006. Visualization of degradable worm micelle breakdown in relation to drug release. Polymer 47: 2519–2525.Google Scholar
  51. Ghosh, S., Basu, S., and Thayumanavan, S. 2006. Simultaneous and reversible functionalization of copolymers for biological applications. Macromolecules 39: 5595–5597.ADSGoogle Scholar
  52. Giacomelli, C., et al. 2006. Phosphorylcholine-based pH-responsive diblock copolymer micelles as drug delivery vehicles: light scattering, electron microscopy, and fluorescence experiments. Biomacromolecules 7: 817–828.PubMedGoogle Scholar
  53. Gillies, E. R. and Frechet, J. M. 2003. A new approach towards acid sensitive copolymer micelles for drug delivery. Chem. Commun. 14: 1640–1641.Google Scholar
  54. Gillies, E. R. and Frechet, J. M. 2005. pH-Responsive copolymer assemblies for controlled release of doxorubicin. Bioconjug. Chem. 16: 361–368.PubMedGoogle Scholar
  55. Gillies, E. R., Jonsson, T. B., and Frechet, J. M. J. 2004. Stimuli-responsive supramolecular assemblies of linear-dendritic copolymers. J. Am. Chem. Soc. 126: 11936–11943.PubMedGoogle Scholar
  56. Gohy, J. F., et al. 2000. Water-soluble complexes formed by sodium poly(4-styrenesulfonate) and a poly(2-vinylpyridinium)-block-poly(ethyleneoxide) copolymer. Macromolecules 33: 9298–9305.ADSGoogle Scholar
  57. Goodwin, A. P., et al. 2005. Synthetic micelle sensitive to IR light via a two-photon process. J. Am. Chem. Soc. 127: 9952–9953.PubMedGoogle Scholar
  58. Gros, L., Ringsdorf, H., and Schupp, H. 1981. Polymeric antitumor agents on a molecular and on a cellular level? Angew. Chem. Int. Ed. Engl. 20: 305–325.Google Scholar
  59. Haag, R. 2004. Supramolecular drug delivery systems based on polymeric core-shell architectures. Angew. Chem. Int. Ed. Engl. 43: 278–282.PubMedGoogle Scholar
  60. Hagan, S. A., et al. 1996. Polylactide-poly(ethylene glycol) copolymers as drug delivery systems. 1. Characterization of water dispersible micelle-forming systems. Langmuir 12: 2153–2161.Google Scholar
  61. Hamaguchi, T., et al. 2005. NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel. Br. J. Cancer 92: 1240–1246.PubMedMathSciNetGoogle Scholar
  62. Harada, A. and Kataoka, K. 1995. Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly(ethylene glycol) segments. Macromolecules 28: 5294–5299.ADSGoogle Scholar
  63. Harada, A. and Kataoka, K. 1999. Chain length recognition: core-shell supramolecular assembly from oppositely charged block copolymers. Science 283: 65–67.PubMedADSGoogle Scholar
  64. Harada, A. and Kataoka, K. 2006. Supramolecular assemblies of block copolymers in aqueous media as nanocontainers relevant to biological applications. Prog. Polym. Sci. 31: 949–982.Google Scholar
  65. Heller, J. and Barr, J. 2004. Poly(ortho esters)–from concept to reality. Biomacromolecules 5: 1625–1632.PubMedGoogle Scholar
  66. Heller, J., et al. 2002. Poly(ortho esters): synthesis, characterization, properties and uses. Adv. Drug Deliv. Rev. 54: 1015–1039.PubMedGoogle Scholar
  67. Heskins, M. and Guillet, J. E. 1968. Solution properties of poly (N-isopropylacrylamide). J. Macromol. Sci. A2: 1441–1455.Google Scholar
  68. Hobbs, S. K., et al. 1998. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc. Natl. Acad. Sci. USA 95: 4607–4612.PubMedADSGoogle Scholar
  69. Hoffman, A. S., et al. 2000. Really smart bioconjugates of smart polymers and receptor proteins. J. Biomed. Mater. Res. 52: 577–586.PubMedGoogle Scholar
  70. Hruby, M., Konak, C., and Ulbrich, K. 2005. Polymeric micellar pH-sensitive drug delivery system for doxorubicin. J. Control. Release 103: 137–148.PubMedGoogle Scholar
  71. Hruby, M., et al. 2007. New bioerodable thermoresponsive polymers for possible radiotherapeutic applications. J. Control. Release 119: 25–33.PubMedGoogle Scholar
  72. Hsiue, G. H., et al. 2006. Environmental-sensitive micelles based on poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) diblock copolymer for application in drug delivery. Int. J. Pharm. 317: 69–75.PubMedGoogle Scholar
  73. Hu, F. -Q., et al. 2006. Shell cross-linked stearic acid grafted chitosan oligosaccharide self-aggregated micelles for controlled release of paclitaxel. Colloid Surf. B 50: 97–103.ADSGoogle Scholar
  74. Hu, Y., et al. 2004. Degradation behavior of poly(H-caprolactone-b-poly(ethylene glycol)-b-poly(–caprolactone) micelles in aqueous solution. Biomacromolecules 5: 1756–1762.PubMedGoogle Scholar
  75. Hu, Y., et al. 2007. Effect of PEG conformation and particle size on the cellular uptake efficiency of nanoparticles with the HepG2 cells. J. Control. Release 118: 7–17.PubMedGoogle Scholar
  76. Huang, X., Rong, F. D., and Li, J. Z. 2007. Novel acid-labile, thermoresponsive poly(methacrylamide) s with pendent ortho ester moieties. Macromol. Rapid Commun. 28: 597–603.Google Scholar
  77. Huh, K. M., et al. 2005. Hydrotropic polymer micelle system for delivery of paclitaxel. J. Control. Release 101: 59–68.PubMedGoogle Scholar
  78. Iijima, M., et al. 1999. Core-polymerized reactive micelles from heterotechelic amphiphilic block copolymers. Macromolecules 32: 1140–1146.ADSGoogle Scholar
  79. Illum, L., et al. 1987. Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages. Biomaterials 8: 113–117.PubMedGoogle Scholar
  80. Inoue, T., et al. 1998. An AB block copolymer of oligo(methyl methacrylate) and poly(acrylic acid) for micellar delivery of hydrophobic drugs. J. Control. Release 51: 221–229.PubMedGoogle Scholar
  81. Ishida, T., Harashima, H., and Kiwada, H. 2002. Liposome clearance. Biosci. Rep. 22: 197–224.PubMedGoogle Scholar
  82. Ivanov, A. E., et al. 2002. Photosensitive copolymer of N-isopropylacrylamide and methacryloyl derivative of spyrobenzopyran. Polymer 43: 3819–3823.Google Scholar
  83. Jaturanpinyo, M., et al. 2004. Preparation of bionanoreactor based on core-shell structured polyion complex micelles entrapping trypsin in the core cross-linked with glutaraldehyde. Bioconjug. Chem. 15: 344–348.PubMedGoogle Scholar
  84. Jeong, B., et al. 1997. Biodegradable block copolymers as injectable drug-delivery systems. Nature 388: 860–862.PubMedADSGoogle Scholar
  85. Jeong, J. H., et al. 2005a. Biodegradable poly(asparagine) grafted with poly(caprolactone) and the effect of substitution on self-aggregation. Colloid Surf. A 264: 187–194.Google Scholar
  86. Jeong, Y. I., et al. 2005b. Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(gamma-benzyl L-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety. Int. J. Pharm. 296: 151–161.PubMedGoogle Scholar
  87. Jiang, J., Tong, X., and Zhao, Y. 2005. A new design for light-breakable polymer micelles. J. Am. Chem. Soc. 127: 8290–8291.PubMedGoogle Scholar
  88. Jiang, J., et al. 2006a. Toward photocontrolled release using light-dissociable block copolymer micelles. Macromolecules 39: 4633–4640.ADSGoogle Scholar
  89. Jiang, X., et al. 2006b. UV irradiation-induced shell cross-linked micelles with pH-responsive cores using ABC triblock copolymers. Macromolecules 39: 5987–5994.ADSGoogle Scholar
  90. Jiang, J., et al. 2007. Polymer micelles stabilization on demand through reversible photo-cross-linking. Macromolecules 40: 790–792.ADSGoogle Scholar
  91. Jones, M. -C. and Leroux, J. -C. 1999. Polymeric micelles–a new generation of colloidal drug carriers. Eur. J. Pharm. Biopharm. 48: 101–111.PubMedGoogle Scholar
  92. Joralemon, M. J., et al. 2005. Shell click-crosslinked (SCC) nanoparticles: a new methodology for synthesis and orthogonal functionalization. J. Am. Chem. Soc. 127: 16892–16899.PubMedGoogle Scholar
  93. Kabanov, A. V., et al. 1992. A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain. J. Control. Release 22: 141–157.Google Scholar
  94. Kabanov, A. V., et al. 1996. Soluble stoichiometric complexes from poly(N-ethyl-4-vinylpyridinium) cations and poly(ethylene oxide)-block-polymethacrylate anions. Macromolecules 29: 6797–6802.ADSGoogle Scholar
  95. Kabanov, A. V., Batrakova, E. V., and Alakhov, V. Y. 2002a. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J. Control. Release 82: 189–212.PubMedGoogle Scholar
  96. Kabanov, A. V., Batrakova, E. V., and Alakhov, V. Y. 2002b. Pluronic block copolymers for overcoming drug resistance in cancer. Adv. Drug Deliv. Rev. 54: 759–779.PubMedGoogle Scholar
  97. Kakizawa, Y., Harada, A., and Kataoka, K. 1999. Environment-sensitive stabilization of core-shell structured polyion complex micelle by reversible cross-linking of the core through disulfide bond. J. Am. Chem. Soc. 121: 11247–11248.Google Scholar
  98. Kakizawa, Y., Harada, A., and Kataoka, K. 2001. 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.PubMedGoogle Scholar
  99. Kang, N., et al. 2005. Stereocomplex block copolymer micelles: core-shell nanostructures with enhanced stability. Nano Lett. 5: 315–319.PubMedADSGoogle Scholar
  100. Kataoka, K., et al. 2000. Doxorubicin-loaded poly(ethylene glycol)-poly([beta]-benzyl-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J. Control. Release 64: 143–153.PubMedGoogle Scholar
  101. Kataoka, K., Harada, A., and Nagasaki, Y. 2001. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv. Drug Deliv. Rev. 47: 113–131.PubMedGoogle Scholar
  102. Katayama, Y., Sonoda, T., and Maeda, M. 2001. A polymer micelle responding to the protein kinase A signal. Macromolecules 34: 8569–8573.ADSGoogle Scholar
  103. Kato, K., et al. 2006. Phase I study of NK105, a paclitaxel-incorporating micellar nanoparticle, in patients with advanced cancer. J. Clin. Oncol. 24: 2018.Google Scholar
  104. Kim, C., et al. 2000. Amphiphilic diblock copolymers based on poly(2-ethyl-2-oxazoline) and poly(1, 3-trimethylene carbonate): Synthesis and micellar characteristics. Macromolecules 33: 7448–7452.ADSGoogle Scholar
  105. Kim, J., et al. 1999. Core-stabilized polymeric micelle as potential drug carrier: increased solubilization of taxol. Polym. Adv. Technol. 10: 647–654.ADSGoogle Scholar
  106. Kim, S. C., et al. 2001. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J. Control. Release 72: 191–202.PubMedGoogle Scholar
  107. Kim, S. Y., et al. 1998. Methoxy poly(ethylene glycol) and epsilon-caprolactone amphiphilic block copolymeric micelle containing indomethacin. II. Micelle formation and drug release behaviours. J. Control. Release 51: 13–22.PubMedGoogle Scholar
  108. Kim, T. Y., et al. 2004. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin. Cancer Res. 10: 3708–3716.PubMedGoogle Scholar
  109. Klibanov, A. L., et al. 1990. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 268: 235–237.PubMedGoogle Scholar
  110. Kohori, F., et al. 1999. Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide)-b-poly(-lactide). Colloid Surf. B 16: 195–205.Google Scholar
  111. Konak, C., et al. 1998. Photoassociation of water-soluble copolymers containing photochromic spirobenzopyran moieties. Polym. Adv. Technol. 9: 641–648.Google Scholar
  112. Konan-Kouakou, Y. N., et al. 2005. In vitro and in vivo activities of verteporfin-loaded nanoparticles. J. Control. Release 103: 83–91.PubMedGoogle Scholar
  113. Kono, K., Nishihara, Y., and Takagishi, T. 1995. Photoresponsive permeability of polyelectrolyte complex capsule membrane containing triphenylmethane leucohydroxide residues. J. Appl. Polym. Sci. 56: 707–713.Google Scholar
  114. Kopelman, R., et al. 2005. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer. J. Magn. Magn. Mater. 293: 404–410.ADSGoogle Scholar
  115. Kreuter, J. 2006. Nanoparticles–a historical perspective. Int. J. Pharm. 331: 1–10.PubMedGoogle Scholar
  116. Krishnadas, A., Rubinstein, I., and Önyüksel, H. 2003. Sterically stabilized phospholipid mixed micelles: in vitro evaluation as a novel carrier for water-insoluble drugs. Pharm. Res. 20: 297–302.PubMedGoogle Scholar
  117. Kumar, N., Ravikumar, M. N., and Domb, A. J. 2001. Biodegradable block copolymers. Adv. Drug Deliv. Rev. 53: 23–44.PubMedGoogle Scholar
  118. Kwon, G., et al. 1994. Enhanced tumor accumulation and prolonged circulation times of micelle-forming poly (ethylene oxide-aspartate) block copolymer–adriamycin conjugates. J. Control. Release 29: 17–23.Google Scholar
  119. Kwon, G. S. 2003. Polymeric micelles for delivery of poorly water-soluble compounds. Crit. Rev. Ther. Drug Carrier Syst. 20: 357–403.PubMedGoogle Scholar
  120. Kwon, G. S. and Okano, T. 1996. Polymeric micelles as new drug carriers. Adv. Drug Deliv. Rev. 21: 107–116.Google Scholar
  121. Kwon, G. S., et al. 1993a. Micelles based on AB block copolymers of poly(ethylene oxide) and poly(b-benzyl l-aspartate). Langmuir 9: 945–949.Google Scholar
  122. Kwon, G. S., et al. 1993b. Biodistribution of micelle-forming polymer-drug conjugates. Pharm. Res. 10: 970–974.PubMedGoogle Scholar
  123. Laschewsky, A. and Rekai, E. D. 2000. Photochemical modification of the lower critical solution temperature of cinnamoylated poly(N-2-hydropropylmethacrylamide) in water. Macromol. Rapid Commun. 21: 937–940.Google Scholar
  124. Lavasanifar, A., Samuel, J., and Kwon, G. S. 2001. The effect of alkyl core structure on micellar properties of poly(ethylene oxide)-block-poly(-aspartamide) derivatives. Colloid Surf. B 22: 115–126.Google Scholar
  125. Lavasanifar, A., et al. 2002. Block copolymer micelles for the encapsulation and delivery of amphotericin B. Pharm. Res. 19: 418–422.PubMedGoogle Scholar
  126. Lavasanifar, A., Samuel, J., and Kwon, G. S. 2002a. The effect of fatty acid substitution on the in vitro release of amphotericin B from micelles composed of poly(ethylene oxide)-block-poly(N-hexyl stearate–aspartamide). J. Control. Release 79: 165–172.PubMedGoogle Scholar
  127. Lavasanifar, A., Samuel, J., and Kwon, G. S. 2002b. Poly(ethylene oxide)-block-poly(-amino acid) micelles for drug delivery. Adv. Drug Deliv. Rev. 54: 169–190.PubMedGoogle Scholar
  128. Laverman, P., et al. 2000. Preclinical and clinical evidence for disappearance of long-circulating characteristics of polyethylene glycol liposomes at low lipid dose. J. Pharmacol. Exp. Ther. 293: 996–1001.PubMedGoogle Scholar
  129. Le Garrec, D., et al. 2002. Optimizing pH-responsive polymeric micelles for drug delivery in a cancer photodynamic therapy model. J. Drug Target. 10: 429–437.PubMedGoogle Scholar
  130. Le Garrec, D., et al. 2004. Poly(N-vinylpyrrolidone)-block-poly(D, L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation. J. Control. Release 99: 83–101.PubMedGoogle Scholar
  131. Lecommandoux, S., et al. 2006a. Smart hybrid magnetic self-assembled micelles and hollow capsules. Prog. Solid State Ch. 34: 171–179.Google Scholar
  132. Lecommandoux, S., et al. 2006b. Self-assemblies of magnetic nanoparticles and di-block copolymers: magnetic micelles and vesicles. J. Magn. Magn. Mater. 300: 71–74.ADSGoogle Scholar
  133. Lee, A. S., et al. 1999a. Characterizing the structure of pH dependent polyelectrolyte block copolymer micelles. Macromolecules 32: 4302–4310.ADSGoogle Scholar
  134. Lee, B. H. and Vernon, B. 2005. Copolymers of N-isopropylacrylamide HEMA-lactate and acrylic acid with time-dependent lower critical solution temperature as a bioresorbable carrier. Polym. Int. 54: 418–422.Google Scholar
  135. Lee, B. H., et al. 2006. In-situ injectable physically and chemically gelling NIPAAm-based copolymer system for embolization. Biomacromolecules 7: 2059–2064.PubMedGoogle Scholar
  136. Lee, E. S., Na, K., and Bae, Y. H. 2003. Polymeric micelle for tumor pH and folate-mediated targeting. J. Control. Release 91: 103–113.PubMedGoogle Scholar
  137. Lee, E. S., et al. 2003a. Poly(-histidine)-PEG block copolymer micelles and pH-induced destabilization. J. Control. Release 90: 363–374.PubMedGoogle Scholar
  138. Lee, E. S., Na, K., and Bae, Y. H. 2005. Super pH sensitive multifunctional polymeric micelle. Nano Lett. 5: 325–329.PubMedADSGoogle Scholar
  139. Lee, J., et al. 2003b. Hydrotropic solubilization of paclitaxel: analysis of chemical structures for hydrotropic property. Pharm. Res. 20: 1022–1030.PubMedGoogle Scholar
  140. Lee, K. Y., Ha, W. S., and Park, W. H. 1995. Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. Biomaterials 16: 1211–1216.PubMedGoogle Scholar
  141. Lee, S. C. and Lee, H. J. 2007. pH-Controlled, polymer-mediated assembly of polymer micelle nanoparticles. Langmuir 23: 488–495.PubMedGoogle Scholar
  142. Lee, S. C., et al. 1999b. Synthesis and micellar characterization of amphiphilic diblock copolymers based on poly(2-ethyl-2-oxazoline) and aliphatic polyesters. Macromolecules 32: 1847–1852.ADSGoogle Scholar
  143. Lee, S. C., et al. 2007. Hydrotropic polymeric micelles for enhanced paclitaxel solubility: in vitro and in vivo characterization. Biomacromolecules 8: 202–208.PubMedGoogle Scholar
  144. Lele, B. S. and Leroux, J. -C. 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: 6714–6723.ADSGoogle Scholar
  145. Lemarchand, C., Gref, R., and Couvreur, P. 2004. Polysaccharide-decorated nanoparticles. Eur. J. Pharm. Biopharm. 58: 327–341.PubMedGoogle Scholar
  146. Lemarchand, C., et al. 2005. Physico-chemical characterization of polysaccharide-coated nanoparticles. J. Control. Release 108: 97–111.PubMedGoogle Scholar
  147. Lemarchand, C., et al. 2006. Influence of polysaccharide coating on the interactions of nanoparticles with biological systems. Biomaterials 27: 108–118.PubMedGoogle Scholar
  148. Leroux, J., et al. 1995. An investigation on the role of plasma and serum opsonins on the internalization of biodegradable poly(D, L-lactic acid) nanoparticles by human monocytes. Life Sci. 57: 695–703.PubMedGoogle Scholar
  149. Letchford, K., et al. 2004. Synthesis and micellar characterization of short block length methoxy poly(ethylene glycol)-block-poly(caprolactone) diblock copolymers. Colloid Surf. B 35: 81–91.Google Scholar
  150. Li, X., Ji, J. and Shen, J. 2006. Synthesis of hydroxyl-capped comb-like poly(ethylene glycol) to develop shell cross-linkable micelles. Polymer 47: 1987–1994.Google Scholar
  151. Li, Y., et al. 2006a. Synthesis of reversible shell cross-linked micelles for controlled release of bioactive agents. Macromolecules 39: 2726–2728.ADSGoogle Scholar
  152. Li, Z., et al. 2006b. Molecularly imprinted polymeric nanospheres by diblock copolymer self-assembly. Macromolecules 39: 2629–2636.ADSGoogle Scholar
  153. Licciardi, M., et al. 2006. New folate-functionalized biocompatible block copolymer micelles as potential anti-cancer drug delivery systems. Polymer 47: 2946–2955.Google Scholar
  154. Liggins, R. T. and Burt, H. M. 2002. Polyether-polyester diblock copolymers for the preparation of paclitaxel loaded polymeric micelle formulations. Adv. Drug Deliv. Rev. 54: 191–202.PubMedGoogle Scholar
  155. Lin, W. J., Juang, L. W., and Lin, C. C. 2003. Stability and release performance of a series of pegylated copolymeric micelles. Pharm. Res. 20: 668–673.PubMedGoogle Scholar
  156. Lin, W. J., et al. 2005. Characterization of pegylated copolymeric micelles and in vivo pharmacokinetics and biodistribution studies. J. Biomed. Mater. Res. B 77: 188–194.Google Scholar
  157. Liu, D.- Z., et al. 2007a. Synthesis, characterization and drug delivery behaviors of new PCP polymeric micelles. Carbohydr. Polym. 68: 544–554.Google Scholar
  158. Liu, J., Xiao, Y., and Allen, C. 2004. Polymer-drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine. J. Pharm. Sci. 93: 132–143.PubMedGoogle Scholar
  159. Liu, J., Zeng, F., and Allen, C. 2005. Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent. J. Control. Release 103: 481–497.PubMedGoogle Scholar
  160. Liu, J., Zeng, F., and Allen, C. 2007. In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration. Eur. J. Pharm. Biopharm. 65: 309–319.PubMedGoogle Scholar
  161. Liu, S., et al. 2002a. Synthesis of shell cross-linked micelles with pH-responsive cores using ABC triblock copolymers. Macromolecules 35: 6121–6131.ADSGoogle Scholar
  162. Liu, S., et al. 2002b. Synthesis of pH-responsive shell crosslinked micelles and their use as nanoreactors for the preparation of gold nanoparticles. Langmuir 18: 8350–8357.Google Scholar
  163. Liu, S. -Q., et al. 2007b. Bio-functional micelles self-assembled from a folate-conjugated block copolymer for targeted intracellular delivery of anticancer drugs. Biomaterials 28: 1423–1433.PubMedGoogle Scholar
  164. Liu, X. -M., et al. 2004. The effect of salt and pH on the phase-transition behaviors of temperature-sensitive copolymers based on N-isopropylacrylamide. Biomaterials 25: 5659–5666.PubMedGoogle Scholar
  165. Lo, C. L., et al. 2007. Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery. Biomaterials 28: 1225–1235.PubMedGoogle Scholar
  166. Lukyanov, A. N. and Torchilin, V. P. 2004. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv. Drug Deliv. Rev. 56: 1273–1289.PubMedGoogle Scholar
  167. Luo, L., et al. 2002. Cellular internalization of poly(ethylene oxide)-b-poly(epsilon-caprolactone) diblock copolymer micelles. Bioconjug. Chem. 13: 1259–1265.PubMedGoogle Scholar
  168. Luo, L., 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: 4008–4013.ADSGoogle Scholar
  169. Maeda, H., et al. 2000. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release 65: 271–284.PubMedGoogle Scholar
  170. Maeda, H., et al. 2003. Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int. Immunopharmacol. 3: 319–328.PubMedGoogle Scholar
  171. Mahmud, A., Xiong, X. B., and Lavasanifar, A. 2006. Novel self-associating poly(ethylene oxide)-block-poly(e-caprolactone) block copolymers with functional side groups on the polyester block for drug delivery. Macromolecules 39: 9419–9428.ADSGoogle Scholar
  172. Mart, R. J., et al. 2006. Peptide-based stimuli-responsive biomaterials. Soft Matter. 2: 822–835.Google Scholar
  173. Martin, T. J., et al. 1996. pH-dependent micellization of poly(2-vinylpyridine)-block-poly(ethylene oxide). Macromolecules 29: 6071–6073.ADSGoogle Scholar
  174. Maruyama, A., et al. 1994a. Preparation of nanoparticles bearing high density carbohydrate chains using carbohydrate-carrying polymers as emulsifier. Biomaterials 15: 1035–1042.PubMedGoogle Scholar
  175. Maruyama, K., et al. 1994b. Phosphatidyl polyglycerols prolong liposome circulation in vivo. Int. J. Pharm. 111: 103–107.Google Scholar
  176. Matsumura, Y. and Maeda, H. 1986. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46: 6387–6392.PubMedGoogle Scholar
  177. Matsumura, Y., et al. 2004. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br. J. Cancer 91: 1775–1781.PubMedGoogle Scholar
  178. Maysinger, D., et al. 2007. Fate of micelles and quantum dots in cells. Eur. J. Pharm. Biopharm. 65: 270–281.PubMedGoogle Scholar
  179. Mertoglu, M., et al. 2005. Stimuli responsive amphiphilic block copolymers for aqueous media synthesised via reversible addition fragmentation chain transfer polymerisation (RAFT). Polymer 46: 7726–7740.Google Scholar
  180. Metselaar, J. M., et al. 2003. A novel family of L-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug. Chem. 14: 1156–1164.PubMedGoogle Scholar
  181. Michel, R., et al. 2005. Influence of PEG architecture on protein adsorption and conformation. Langmuir 21: 12327–12332.PubMedGoogle Scholar
  182. Moghimi, S. M. and Szebeni, J. 2003. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog. Lipid Res. 42: 463–478.PubMedGoogle Scholar
  183. Moghimi, S. M., et al. 1991a. Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem. Biophys. Res. Commun. 177: 861–866.PubMedGoogle Scholar
  184. Moghimi, S. M., et al. 1991b. The effect of poloxamer-407 on liposome stability and targeting to bone marrow: comparison with polystyrene microspheres. Int. J. Pharm. 68: 121–126.Google Scholar
  185. Moghimi, S. M., Hunter, A. C., and Murray, J. C. 2001. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol. Rev. 53: 283–318.PubMedGoogle Scholar
  186. Molineux, G. 2002. PEGylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat. Rev. 28: 13–16.PubMedGoogle Scholar
  187. Moses, M. A., Brem, H., and Langer, R. 2003. Advancing the field of drug delivery: taking aim at cancer. Cancer Cell 4: 337–341.PubMedGoogle Scholar
  188. Na, K. and Bae, K. H. 2002. Self-assembled hydrogel nanoparticles responsive to tumor extracellular pH from pullulan derivative/sulfonamide conjugate: characterization, aggregation, and adriamycin release in vitro. Pharm. Res. 19: 681–688.PubMedGoogle Scholar
  189. Na, K., Lee, K. H., and Bae, Y. H. 2004. pH-sensitivity and pH-dependent interior structural change of self-assembled hydrogel nanoparticles of pullulan acetate/oligo-sulfonamide conjugate. J. Control. Release 97: 513–525.PubMedGoogle Scholar
  190. Nakamura, E., et al. 2006. A polymeric micelle MRI contrast agent with changeable relaxivity. J. Control. Release 114: 325–333.PubMedGoogle Scholar
  191. Nakanishi, T., et al. 2001. Development of the polymer micelle carrier system for doxorubicin. J. Control. Release 74: 295–302.PubMedGoogle Scholar
  192. Nam, Y. S., et al. 2003. New micelle-like polymer aggregates made from PEI-PLGA diblock copolymers: micellar characteristics and cellular uptake. Biomaterials 24: 2053–2059.PubMedGoogle Scholar
  193. Neradovic, D., et al. 1999. Poly(N-isopropylacrylamide) with hydrolyzable lactic acid ester side groups: a new type of thermosensitive polymer. Macromol. Rapid Commun. 20: 577–581.Google Scholar
  194. Neradovic, D., Van Nostrum, C. F., and Hennink, W. E. 2001. Thermoresponsive polymeric micelles with controlled instability based on hydrolytically sensitive N-isopropylacrylamide copolymers. Macromolecules 34: 7589–7591.ADSGoogle Scholar
  195. Neradovic, D., 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: 2409–2418.PubMedGoogle Scholar
  196. Nishiyama, N. and Kataoka, K. 2006. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. Pharmacol. Therapeut. 112: 630–648.Google Scholar
  197. Nishiyama, N., et al. 2001. Cisplatin-loaded polymer-metal complex micelle with time-modulated decaying property as a novel drug delivery system. Pharm. Res. 18: 1035–1041.PubMedGoogle Scholar
  198. Nishiyama, N., et al. 2003. Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer Res. 63: 8977–8983.PubMedGoogle Scholar
  199. Oku, N. and Namba, Y. 1994. Long-circulating liposomes. Crit. Rev. Ther. Drug 11: 231–270.Google Scholar
  200. Opanasopit, P., et al. 2004. Block copolymer design for camptothecin incorporation into polymeric micelles for passive tumor targeting. Pharm. Res. 21: 2001–2008.PubMedGoogle Scholar
  201. Opanasopit, P., et al. 2005. Influence of serum and albumins from different species on stability of camptothecin-loaded micelles. J. Control. Release 104: 313–321.PubMedGoogle Scholar
  202. O’Reilly, R. K., Hawker, C. J., and Wooley, K. L. 2006. Cross-linked block copolymer micelles: functional nanostructures of great potential and versatility. Chem. Soc. Rev. 35: 1068–1083.PubMedGoogle Scholar
  203. Otsuka, H., Nagasaki, Y., and Kataoka, K. 2003. PEGylated nanoparticles for biological and pharmaceutical applications. Adv. Drug Deliv. Rev. 55: 403–419.PubMedGoogle Scholar
  204. Owens, D. E., 3rd and Peppas, N. A. 2006. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 307: 93–102.PubMedGoogle Scholar
  205. Park, E. K., et al. 2005. Folate-conjugated methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric micelles for tumor-targeted drug delivery. J. Control. Release 109: 158–168.PubMedGoogle Scholar
  206. Park, J. S. and Kataoka, K. 2006. Precise control of lower critical solution temperature of thermosensitive poly(2-isopropyl-2-oxazoline) via gradient copolymerization with 2-ethyl-2-oxazoline as a hydrophilic comonomer. Macromolecules 39: 6622–6630.ADSGoogle Scholar
  207. Park, J. S., et al. 2007. Preparation and characterization of polyion complex micelles with a novel thermosensitive poly(2-isopropyl-2-oxazoline) shell via the complexation of oppositely charged block ionomers. Langmuir 23: 138–146.PubMedGoogle Scholar
  208. Passirani, C., et al. 1998. Long-circulating nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate). Pharm. Res. 15: 1046–1050.PubMedGoogle Scholar
  209. Pelton, R. 2000. Temperature-sensitive aqueous microgels. Adv. Colloid Interface 85: 1–33.Google Scholar
  210. Peracchia, M. T., et al. 1997. Complement consumption by poly(ethylene glycol) in different conformations chemically coupled to poly(isobutyl 2-cyanoacrylate) nanoparticles. Life Sci. 61: 749–761.PubMedGoogle Scholar
  211. Petrov, P., Bozukov, M., and Tsvetanov, C. B. 2005. Innovative approach for stabilizing poly(ethylen oxide)-b-poly(propylene oxide)-b-poly(ethylen oxide) micelles by forming nano-sized networks in the micelle. J. Mater. Chem. 15: 1481–1486.Google Scholar
  212. Pilon, L. N., et al. 2005. Synthesis and characterization of shell cross-linked micelles with hydroxy-functional coronas: a pragmatic alternative to dendrimers? Langmuir 21: 3808–3813.PubMedGoogle Scholar
  213. Piskin, E. 2004. Molecularly designed water soluble, intelligent, nanosize polymeric carriers. Int. J. Pharm. 277: 105–118.PubMedGoogle Scholar
  214. Prompruk, K., et al. 2005. Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier. Int. J. Pharm. 297: 242–253.PubMedGoogle Scholar
  215. Qiu, X. P. and Wu, C. 1997. Study of the core-shell nanoparticle formed through the “coil-to-globule” transition of poly(N-isopropylacrylamide) grafted with poly(ethylene oxide). Macromolecules 30: 7921–7926.ADSGoogle Scholar
  216. Rapoport, N. 2004. Combined cancer therapy by micellar-encapsulated drug and ultrasound. Int. J. Pharm. 277: 155–162.PubMedGoogle Scholar
  217. Rapoport, N., et al. 2002. Intracellular uptake and trafficking of pluronic micelles in drug-sensitive and MDR cells: effect on the intracellular drug localization. J. Pharm. Sci. 91: 157–170.PubMedGoogle Scholar
  218. Rapoport, N., et al. 2003. Drug delivery in polymeric micelles: from in vitro to in vivo. J. Control. Release 91: 85–95.PubMedGoogle Scholar
  219. Rapoport, N. Y., et al. 2004. Ultrasound-triggered drug targeting of tumors in vitro and in vivo. Ultrasonics 42: 943–950.PubMedGoogle Scholar
  220. Ravi, P., et al. 2005. New water-soluble azobenzene-containing diblock copolymers: synthesis and aggregation behavior. Polymer 46: 137–146.Google Scholar
  221. Reddy, G. R., et al. 2006. Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin. Cancer Res. 12: 6677–6686.PubMedGoogle Scholar
  222. Rheingans, O., et al. 2000. Nanoparticles built of cross-linked heterotechelic amphiphilic poly(dimethylsiloxane)-b-poly(ethylene oxide) diblock copolymers. Macromolecules 33: 4780–4790.ADSGoogle Scholar
  223. Rijcken, C. J. F., et al. 2005. Novel fast degradable thermosensitive polymeric micelles based on PEG-block-poly(N-(2-hydroxyethyl) methacrylamide-oligolactates). Biomacromolecules 6: 2343–2351.PubMedGoogle Scholar
  224. Rijcken, C. J. F., Soga, O., Hennink, W. E., and van Nostrum, C. F. 2007. Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: An attractive tool for drug delivery. J. Control. Release 120:131–148.PubMedGoogle Scholar
  225. Rijcken, C. J. F., Snel, C. J., Schiffelers, R. M., van Nostrum, C. F., and Hennink, W. E. (2007). Hydrolyzable core crosslinked polymeric micelles. synthesis, characterisation and in vivo studies. Biomaterials 28:5581–5593.PubMedGoogle Scholar
  226. Rodriguez-Hernandez, J., et al. 2005a. Preparation of shell cross-linked nano-objects from hybrid-peptide block copolymers. Biomacromolecules 6: 2213–2220.PubMedGoogle Scholar
  227. Rodriguez-Hernandez, J., et al. 2005b. Toward ‘smart’ nano-objects by self-assembly of block copolymers in solution. Prog. Polym. Sci. 30: 691–724.Google Scholar
  228. Romberg, B., et al. 2007. Pharmacokinetics of poly(hydroxyethyl-L-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration. Biochim. Biophys. Acta 1768: 737–743.PubMedGoogle Scholar
  229. Rosler, A., Vandermeulen, G. W., and Klok, H. A. 2001. Advanced drug delivery devices via self-assembly of amphiphilic block copolymers. Adv. Drug Deliv. Rev. 53: 95–108.PubMedGoogle Scholar
  230. Rouzes, C., et al. 2000. Surface modification of poly(lactic acid) nanospheres using hydrophobically modified dextrans as stabilizers in an o/w emulsion/evaporation technique. J. Biomed. Mater. Res. 50: 557–565.PubMedGoogle Scholar
  231. Sahoo, S., Ma, and Labhasetwar 2003. Nanotech approaches to drug delivery and imaging. Drug Discov. Today 8: 1112–1120.PubMedGoogle Scholar
  232. Salgado-Rodriguez, R., Licea-Claverie, A., and Arndt, K. F. 2004. Random copolymers of N-isopropylacrylamide and methacrylic acid monomers with hydrophobic spacers: pH-tunable temperature-sensitive materials. Eur. Polym. J. 40: 1931–1946.Google Scholar
  233. Savic, R., et al. 2006. Assessment of the integrity of poly(caprolactone)-b-poly(ethyleneoxide) micelles under biological conditions: a fluorogenic based approach. Langmuir 22: 3570–3578.PubMedGoogle Scholar
  234. Schild, H. G. 1992. Poly (N-isopropylacrylamide) experiment, theory and application. Prog. Polym. Sci. 17: 163–249.Google Scholar
  235. Senior, J. and Gregoriadis, G. 1982. Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components. Life Sci. 30: 2123–2136.PubMedGoogle Scholar
  236. Sethuraman, V. A. and Bae, Y. H. 2007. TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. J. Control. Release 118: 216–224.PubMedGoogle Scholar
  237. Seymour, L. W., et al. 1987. Effect of molecular weight (Mw) of N-(2-hydroxypropyl) methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats. J. Biomed. Mater. Res. 21: 1341–1358.PubMedGoogle Scholar
  238. Shah, S. S., et al. 1997. Polymer-drug conjugates: manipulating drug delivery kinetics using model LCST systems. J. Control. Release 45: 95–101.Google Scholar
  239. Shi, B., et al. 2005. Stealth MePEG-PCL micelles: effects of polymer composition on micelle physicochemical characteristics, in vitro drug release, in vivo pharmacokinetics in rats and biodistribution in S180 tumor-bearing mice. Colloid Polym. Sci. 283: 954–967.Google Scholar
  240. Shibayama, M., Mizutani, S., and Nomura, S. 1996. Thermal properties of copolymer gels containing N-isopropylacrylamide. Macromolecules 29: 2019–2024.ADSGoogle Scholar
  241. Shuai, X., et al. 2004. Core-cross-linked polymeric micelles as paclitaxel carriers. Bioconjug. Chem. 15: 441–448.PubMedGoogle Scholar
  242. Soga, O., Van Nostrum, C. F., and Hennink, W. E. 2004. Poly(N-2-hydroxypropyl) methacrylamide mono/di lactate): a new class of biodegradable polymers with tuneable thermosensitivity. Biomacromolecules 5: 818–821.PubMedGoogle Scholar
  243. Soga, O., et al. 2004. Physicochemical characterization of degradable thermosensitive polymeric micelles. Langmuir 20: 9388–9395.PubMedGoogle Scholar
  244. Soga, O., et al. 2005. Thermosensitive and biodegradable polymeric micelles for paclitaxel delivery. J. Control. Release 103: 341–353.PubMedGoogle Scholar
  245. Soppimath, K. S., et al. 2001. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Release 70: 1–20.PubMedGoogle Scholar
  246. Soppimath, K. S., Tan, D. C. -W., and Yang, Y. -Y. 2005. pH-triggered thermally responsive polymer core-shell nanoparticles for drug delivery. Adv. Mater. 17: 318–323.Google Scholar
  247. Stolnik, S., Illum, L., and Davis, S. S. 1995. Long circulating microparticulate drug carriers. Adv. Drug Deliv. Rev. 16: 195–214.Google Scholar
  248. Sugiyama, K. and Sono, K. 2000. Characterization of photo- and thermoresponsible amphiphilic copolymers having azobenzene moieties as side groups. J. Appl. Poly. Sci. 81: 3056–3063.Google Scholar
  249. Sun, X., et al. 2005. An assessment of the effects of shell cross linked nanoparticle size, core composition and surface pegylation on in vivo distribution. Biomacromolecules 6: 2541–2554.PubMedGoogle Scholar
  250. Szczubialka, K., et al. 2004. Photocrosslinkable smart terpolymers responding to pH, temperature and ionic strength. J. Polym. Sci. Pol. Chem. 43: 3879–3886.Google Scholar
  251. Takeoka, Y., et al. 1995. Electrochemical control of drug release from redox-active micelles. J. Control. Release 33: 79–87.Google Scholar
  252. Takeuchi, H., et al. 2001. Evaluation of circulation profiles of liposomes coated with hydrophilic polymers having different molecular weights in rats. J. Control. Release 75: 83–91.PubMedGoogle Scholar
  253. Tang, Y., et al. 2003. Solubilization and controlled release of a hydrophobic drug using novel micelle-forming ABC triblock copolymers. Biomacromolecules 4: 1636–1645.PubMedGoogle Scholar
  254. Teng, Y., et al. 1998. Release kinetics studies of aromatic molecules into water from block polymer micelles. Macromolecules 31: 3578–3587.ADSGoogle Scholar
  255. Thurmond, K. B. II., et al. 1999. Shell cross-linked polymer micelles: stabilized assemblies with great versatility and potential. Colloid Surface B 16: 45–54.Google Scholar
  256. Tian, L., et al. 2004. Core crosslinkable polymeric micelles from PEG-lipid amphiphiles as drug carriers. J. Mater. Chem. 14: 2317–2324.Google Scholar
  257. Tong, X., et al. 2005. How can azobenzene block copolymer vesicles be dissociated and reformed by light. J. Phys. Chem. B 109: 20281–20287.PubMedGoogle Scholar
  258. Topp, M. D. C., et al. 1997. Thermosensitive micelle-forming block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide). Macromolecules 30: 8518–8520.ADSGoogle Scholar
  259. Torchilin, V. P. 2001. Structure and design of polymeric surfactant-based drug delivery systems. J. Control. Release 73: 137–172.PubMedGoogle Scholar
  260. Torchilin, V. P. 2002. PEG-based micelles as carriers of contrast agents for different imaging modalities. Adv. Drug Deliv. Rev. 54: 235–252.PubMedGoogle Scholar
  261. Torchilin, V. P. 2004. Targeted polymeric micelles for delivery of poorly soluble drugs. Cell. Mol. Life Sci. 61: 2549–2559.PubMedGoogle Scholar
  262. Torchilin, V. P. 2006. Multifunctional nanocarriers. Adv. Drug Deliv. Rev. 58: 1532–1555.PubMedGoogle Scholar
  263. Torchilin, V. P. 2007. Micellar nanocarriers: pharmaceutical perspectives. Pharm. Res. 24: 1–16.PubMedGoogle Scholar
  264. Torchilin, V. P. and Trubetskoy, V. S. 1995. Which polymers can make nanoparticulate drug carriers long-circulating? Adv. Drug Deliv. Rev. 16: 141–155.Google Scholar
  265. Torchilin, V. P., et al. 2001. Amphiphilic poly-N-vinylpyrrolidones: synthesis, properties and liposome surface modification. Biomaterials 22: 3035–3044.PubMedGoogle Scholar
  266. Torchilin, V. P., et al. 2003. Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs. Proc. Natl. Acad. Sci. USA 100: 6039–6044.PubMedADSGoogle Scholar
  267. Torchilin, V. P., et al. 1994. Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo. Biochim. Biophys. Acta 1195: 181–184.PubMedGoogle Scholar
  268. Trubetskoy, V. S., et al. 1996. Stable polymeric micelles: lymphangiographic contrast media for gamma scintigraphy and magnetic resonance imaging. Acad. Radiol. 3: 232–238.PubMedGoogle Scholar
  269. van Nostrum, C. F. 2004. Polymeric micelles to deliver photosensitizers for photodynamic therapy. Adv. Drug Deliv. Rev. 56: 9–16.PubMedGoogle Scholar
  270. Volet, G., et al. 2005. Synthesis of monoalkyl end-capped poly(2-methyl-2-oxazoline) and its micelle formation in aqueous solution. Macromolecules 38: 5190–5197.ADSGoogle Scholar
  271. Vonarbourg, A., et al. 2006a. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27: 4356–4373.PubMedGoogle Scholar
  272. Vonarbourg, A., et al. 2006b. Evaluation of PEGylated lipid nanocapsules versus complement system activation and macrophage uptake. J. Biomed. Mater. Res. 78: 620–628.Google Scholar
  273. Watanabe, M., et al. 2006. Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability. Int. J. Pharm. 308: 183–189.PubMedGoogle Scholar
  274. Weissig, V., Whiteman, K. R., and Torchilin, V. P. 1998. Accumulation of protein-loaded long-circulating micelles and liposomes in subcutaneous lewis lung carcinoma in mice. Pharm. Res. 15: 1552–1556.PubMedGoogle Scholar
  275. Whiteman, K., et al. 2001. Poly(HPMA)-coated liposomes demonstrated prolonged circulation in mice. J. Liposome Res. 11: 153–164.PubMedGoogle Scholar
  276. Wickline, S. A. and Lanza, G. M. 2003. Nanotechnology for molecular imaging and targeted therapy. Circulation 107: 1092–1095.PubMedGoogle Scholar
  277. Wilhelm, M., et al. 1991. Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study. Macromolecules 24: 1033–1040.ADSGoogle Scholar
  278. Woodle, M. C. and Lasic, D. D. 1992. Sterically stabilized liposomes. Biochim. Biophys. Acta 1113: 171–199.PubMedGoogle Scholar
  279. Woodle, M. C., Engbers, C. M., and Zalipsky, S. 1994. New amphipatic polymer-lipid conjugates forming long-circulating reticuloendothelial system-evading liposomes. Bioconjug. Chem. 5: 493–496.PubMedGoogle Scholar
  280. Xie, Z., et al. 2007. A novel polymer-paclitaxel conjugate based on amphiphilic triblock copolymer. J. Control. Release 117: 210–216.PubMedGoogle Scholar
  281. Xiong, X. B., et al. 2007. Conjugation of arginine-glycine-aspartic acid peptides to poly(ethylene oxide)-b-poly(epsilon-caprolactone) micelles for enhanced intracellular drug delivery to metastatic tumor cells. Biomacromolecules 8: 874–884.PubMedGoogle Scholar
  282. Yamamoto, Y., et al. 2001. Long-circulating poly(ethylene glycol)-poly(D, L-lactide) block copolymer micelles with modulated surface charge. J. Control. Release 77: 27–38.PubMedGoogle Scholar
  283. Yi, Y., et al. 2005. A polymeric nanoparticle consisting of mPEG-PLA-Toco and PLMA-COONa as a drug carrier: improvements in cellular uptake and biodistribution. Pharm. Res. 22: 200–208.PubMedGoogle Scholar
  284. Yin, X., Hoffman, A. S., and Stayton, P. S. 2006. Poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH. Biomacromolecules 7: 1381–1385.PubMedGoogle Scholar
  285. Yokoyama, M., et al. 1992. Preparation of micelle-forming polymer-drug conjugates. Bioconjug. Chem. 3: 295–301.PubMedGoogle Scholar
  286. Yokoyama, M., et al. 1994. Improved synthesis of adriamycin-conjugated poly (ethylene oxide)-poly (aspartic acid) block copolymer and formation of unimodal micellar structure with controlled amount of physically entrapped adriamycin. J. Control. Release 32: 269–277.Google Scholar
  287. Yokoyama, M., et al. 1998. Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor. J. Control. Release 50: 79–92.PubMedGoogle Scholar
  288. Yokoyama, M., et al. 1999. Selective delivery of adriamycin to a solid tumor using a polymeric micelle carrier system. J. Drug Target. 7: 171–186.PubMedGoogle Scholar
  289. Yokoyama, M., et al. 2004. Polymer design and incorporation methods for polymeric micelle carrier system containing water-insoluble anti-cancer agent camptothecin. J. Drug Target. 12: 373–384.PubMedGoogle Scholar
  290. Yoon, T. J., et al. 2005. Multifunctional nanoparticles possessing a ‘magnetic motor effect’ for drug or gene delivery. Angew. Chem. Int. Ed. Engl. 117: 1092–1095.Google Scholar
  291. Yoshida, E. and Kunugi, S. 2002. Micelle formation of poly(vinyl phenol)-block-polystyrene by alfa, omega-diamines. J. Polym. Sci. Pol. Chem. 40: 3063–3067.Google Scholar
  292. Yuan, F., et al. 1995. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 55: 3752–3756.PubMedGoogle Scholar
  293. Zamboni, W. C. 2005. Liposomal, nanoparticle and conjugated formulations of anticancer agents. Clin. Cancer Res. 11: 8230–8234.PubMedGoogle Scholar
  294. Zhang, G. -D., et al. 2003. Polyion complex micelles entrapping cationic dendrimer porphyrin: effective photosensitizer for photodynamic therapy of cancer. J. Control. Release 93: 141–150.PubMedGoogle Scholar
  295. Zhang, J., et al. 2006a. Micellization phenomena of amphiphilic block copolymers based on methoxy poly(ethylene glycol) and either crystalline or amorphous poly(caprolactone-b-lactide). Biomacromolecules 7: 2492–2500.PubMedGoogle Scholar
  296. Zhang, L., et al. 2006b. Using the reversible addition-fragmentation chain transfer process to synthesize core-crosslinked micelles. J. Polym. Sci. Pol. Chem. 44: 2177–2194.Google Scholar
  297. Zhang, Z., Grijpma, D. W., and Feijen, J. 2006. Thermo-sensitive transition of monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate) films to micellar-like nanoparticles. J. Control. Release 112: 57–63.PubMedGoogle Scholar
  298. Zhu, P. W. and Napper, D. H. 2000. Effect of heating rate on nanoparticle formation of poly(N-isopropylacrylamide)-poly(ethylene glycol) block copolymer microgels. Langmuir 16: 8543–8545.Google Scholar
  299. Zuccari, G., et al. 2005. Modified polyvinylalcohol for encapsulation of all-trans-retinoic acid in polymeric micelles. J. Control. Release 103: 369–380.PubMedGoogle Scholar
  300. Zweers, M. L. T., et al. 2004. In vitro degradation of nanoparticles prepared from polymers based on DL-lactide, glycolide and poly(ethylene oxide). J. Control. Release 100: 347–356.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Myrra G. Carstens
    • 1
  • Cristianne J. F. Rijcken
    • 1
  • Cornelus F. van Nostrum
    • 1
  • Wim E. Hennink
    • 1
  1. 1.Department of PharmaceuticsUtrecht Institute for Pharmaceutical SciencesNetherlands

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