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Nanogels as Pharmaceutical Carriers

  • Alexander V. Kabanov
  • Serguei V. Vinogradov
Part of the Fundamental Biomedical Technologies book series (FBMT, volume 4)

Nanogels are nanosized networks of chemically or physically cross-linked polymers that swell in a good solvent. The term “nanogel” (NanoGel™) was first introduced by us to define cross-linked bifunctional networks of a polyion and a nonionic polymer for delivery of polynucleotides (cross-linked polyethyleneimine (PEI) and poly(ethylene glycol) (PEG) or PEG-cl-PEI) (Lemieux et al., 2000; Vinogradov et al., 1999). However, some other studies also described nanoparticles of polymeric hydrogels. For example, work by Akiyoshi and Sunamoto proposed nanosized swollen aggregates of cholesterol-modified polysaccharide (pullulan) for delivery of insulin (Akiyoshi et al., 1998). Altogether, nanogels represent a novel family of nanoscale materials for delivery drugs, genes, and imaging agents. Publications using nanogels in pharmaceutics and nanomedicine have greatly increased after 2002 (Fig. 1), when the first review on this subject was published (Vinogradov et al., 2002). This demonstrates an increasing interest in nanogels by biomaterial and pharmaceutical scientists.

Keywords

Atom Transfer Radical Polymerization Atom Transfer Radical Polymerization Nucleoside Analog Inverse Microemulsion Polyelectrolyte Hydrogel 
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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References

  1. Akiyoshi, K., Kobayashi, S., Shichibe, S., Mix, D., Baudys, M., Kim, S. W., and Sunamoto, J., 1998, Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin, J Control Release 54:313–320.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. Bronich, T., Vinogradov, S., and Kabanov, A. V., 2001, Interaction of nanosized copolymer networks with oppositely charged amphiphilic molecules, Nano Lett 1:535–540.CrossRefADSGoogle Scholar
  4. Bronich, T. K., Keifer, P. A., Shlyakhtenko, L. S., and Kabanov, A. V., 2005, Polymer micelle with cross-linked ionic core, J Am Chem Soc 127:8236–8237.PubMedCrossRefGoogle Scholar
  5. Bronich, T. K., Bontha, S., Shlyakhtenko, L. S., Bromberg, L., Hatton, T. A., and Kabanov, A. V., 2006, Template-assisted synthesis of nanogels from pluronic-modified poly(acrylic acid), J Drug Target 14:357–366.PubMedCrossRefGoogle Scholar
  6. Donini, C., Robinson, D. N., Colombo, P., Giordano, F., and Peppas, N. A., 2002, Preparation of poly(methacrylic acid-g-poly(ethylene glycol) ) nanospheres from methacrylic monomers for pharmaceutical applications, Int J Pharm 245:83–91.PubMedCrossRefGoogle Scholar
  7. Daoud-Mahammed, S., Couvreur, P., and Gref, R., 2007, Novel self-assembling nanogels: stability and lyophilisation studies, Int J Pharm 332:185–191.PubMedCrossRefGoogle Scholar
  8. Eichenbaum, G. M., Kiser, P. F., Simon, S. A., and Needham, D., 1998, pH and ion-triggered volume response of anionic hydrogel microspheres, Macromolecules 31:5084–5093.PubMedCrossRefADSGoogle Scholar
  9. Francis, G. E., Delgado, C., Fisher, D., Malik, F., and Agrawal, A. K., 1996, Polyethylene glycol modification: relevance of improved methodology to tumour targeting, J Drug Target 3:321–340.PubMedCrossRefGoogle Scholar
  10. Galmarini, C. M., Mackey, J. R., and Dumontet, C., 2002, Nucleoside analogues and nucleobases in cancer treatment, Lancet Oncol 3:415–424.PubMedCrossRefGoogle Scholar
  11. Goh, S. L., Murthy, N., Xu, M., and Frechet, J. M., 2004, Cross-linked microparticles as carriers for the delivery of plasmid DNA for vaccine development, Bioconjug Chem 15:467–474.PubMedCrossRefGoogle Scholar
  12. Hatse, S., De Clercq, E., and Balzarini, J., 1999, Role of antimetabolites of purine and pyrimidine nucleotide metabolism in tumor cell differentiation, Biochem Pharmacol 58:539–555.PubMedCrossRefGoogle Scholar
  13. Hayashi, H., Iijima, M., Kataoka, K., and Nagasaki, Y., 2005, pH-Sensitive nanogel possessing reactive PEG tethered chains on the surface, Macromolecules 37:5389–5396.CrossRefADSGoogle Scholar
  14. Hennink, W. E. and van Nostrum, C. F., 2002, Novel crosslinking methods to design hydrogels, Adv Drug Deliv Rev 54:13–36.PubMedCrossRefGoogle Scholar
  15. Kabanov, A. V. and Alakhov, V. Y., 2002, Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers, Crit Rev Ther Drug Carrier Syst 19:1–72.PubMedCrossRefGoogle Scholar
  16. Kabanov, V. A., Skobeleva, V. B., Rogacheva, V. B., and Zezin, A. B., 2004, Sorption of proteins by slightly cross-linked polyelectrolyte hydrogels: kinetics and mechanism, J Phys Chem B 108:1485–1490.CrossRefGoogle Scholar
  17. Kato, N., Hasegawa, U., Morimoto, N., Saita, Y., Nakashima, K., Ezura, Y., Kurosawa, H., Akiyoshi, K., and Noda, M., 2007, Nanogel-based delivery system enhances PGE(2) effects on bone formation, J Cell Biochem (in press).Google Scholar
  18. Khmelnitsky, Y. L., Neverova, I. N., Gedrovich, A. V., Polyakov, V. A., Levashov, A. V., and Martinek, K., 1992, Catalysis by alpha-chymotrypsin entrapped into surface-modified polymeric nanogranules in organic solvent, Eur J Biochem 210:751–757.PubMedCrossRefGoogle Scholar
  19. Kohli, E., Han, H. Y., Zeman, A. D., and Vinogradov, S. V., 2007, Formulations of biodegradable Nanogel carriers with 5’-triphosphates of nucleoside analogs that display a reduced cytotoxicity and enhanced drug activity, J Control Release.Google Scholar
  20. Kwon, Y. J., James, E., Shastri, N., and Frechet, J. M., 2005a, In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles, Proc Natl Acad Sci USA 102:18264–18268.PubMedCrossRefADSGoogle Scholar
  21. Kwon, Y. J., Standley, S. M., Goh, S. L., and Frechet, J. M., 2005b, Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles, J Control Release 105:199–212.PubMedCrossRefGoogle Scholar
  22. Kwon, Y. J., Standley, S. M., Goodwin, A. P., Gillies, E. R., and Frechet, J. M., 2005c, Directed antigen presentation using polymeric microparticulate carriers degradable at lysosomal pH for controlled immune responses, Mol Pharm 2:83–91.PubMedCrossRefGoogle Scholar
  23. Lee, H., Mok, H., Lee, S., Oh, Y. K., and Park, T. G., 2007, Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels, J Control Release 119:245–252.PubMedCrossRefGoogle Scholar
  24. Lemieux, P., Vinogradov, S. V., Gebhart, C. L., Guerin, N., Paradis, G., Nguyen, H. K., Ochietti, B., Suzdaltseva, Y. G., Bartakova, E. V., Bronich, T. K., St-Pierre, Y., Alakhov, V. Y., and Kabanov, A. V., 2000, Block and graft copolymers and NanoGel copolymer networks for DNA delivery into cell, J Drug Target 8:91–105.PubMedCrossRefGoogle Scholar
  25. McAllister, K., Sazani, P., Adam, M., Cho, M. J., Rubinstein, M., Samulski, R. J., and DeSimone, J. M., 2002, Polymeric nanogels produced via inverse microemulsion polymerization as potential gene and antisense delivery agents, J Am Chem Soc 124:15198–15207.PubMedCrossRefGoogle Scholar
  26. Missirlis, D., Tirelli, N., and Hubbell, J. A., 2005, Amphiphilic hydrogel nanoparticles. Preparation, characterization, and preliminary assessment as new colloidal drug carriers, Langmuir 21:2605–2613.PubMedCrossRefGoogle Scholar
  27. Missirlis, D., Kawamura, R., Tirelli, N., and Hubbell, J. A., 2006, Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles, Eur J Pharm Sci 29:120–129.PubMedCrossRefGoogle Scholar
  28. Murthy, N., Xu, M., Schuck, S., Kunisawa, J., Shastri, N., and Frechet, J. M., 2003, A macromolecular delivery vehicle for protein-based vaccines: acid-degradable protein-loaded microgels, Proc Natl Acad Sci USA 100:4995–5000.PubMedCrossRefADSGoogle Scholar
  29. Nayak, S., Lee, H., Chmielewski, J., and Lyon, L. A., 2004, Folate-mediated cell targeting and cytotoxicity using thermoresponsive microgels, J Am Chem Soc 126:10258–10259.PubMedCrossRefGoogle Scholar
  30. Ogawa, K., Sato, S., and Kokufuta, E., 2005, Formation of intra- and interparticle polyelectrolyte complexes between cationic nanogel and strong polyanion, Langmuir 21:4830–4836.PubMedCrossRefGoogle Scholar
  31. Ogawa, K., Sato, S., and Kokufuta, E., 2007, On an intraparticle complex of cationic nanogel with a stoichiometric amount of bound polyanions, Langmuir 23:2095–2102.PubMedCrossRefGoogle Scholar
  32. Oh, J. K., Tang, C., Gao, H., Tsarevsky, N. V., and Matyjaszewski, K., 2006, Inverse miniemulsion ATRP: a new method for synthesis and functionalization of well-defined water-soluble/cross-linked polymeric particles, J Am Chem Soc 128:5578–5584.PubMedCrossRefGoogle Scholar
  33. Oh, J. K., Siegwart, D. J., Lee, H. I., Sherwood, G., Peteanu, L., Hollinger, J. O., Kataoka, K., and Matyjaszewski, K., 2007a, Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation, J Am Chem Soc 129:5939–5945.PubMedCrossRefGoogle Scholar
  34. Oh, K. T., Bronich, T. K., Kabanov, V. A., and Kabanov, A. V., 2007b, Block polyelectrolyte networks from poly(acrylic acid) and poly(ethylene oxide): sorption and release of cytochrome C, Biomacromolecules 8:490–497.PubMedCrossRefGoogle Scholar
  35. Park, H., Temenoff, J. S., Tabata, Y., Caplan, A. I., and Mikos, A. G., 2007, Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem cell and growth factor delivery for cartilage tissue engineering, Biomaterials 28:3217–3227.PubMedCrossRefGoogle Scholar
  36. Ricka, J. and Tanaka, T., 1984, Swelling of ionic gels: quantitative performance of the Donnan theory, Macromolecules 17:2916–2921.CrossRefADSGoogle Scholar
  37. Shin, Y., Chang, J. H., Liu, J., Williford, R., Shin, Y., and Exarhos, G. J., 2001, Hybrid nanogels for sustainable positive thermosensitive drug release, J Control Release 73:1–6.PubMedCrossRefGoogle Scholar
  38. Shin, Y., Liu, J., Chang, J. H., and Exarhos, G. J., 2002, Sustained drug release on temperature-responsive poly(N-isopropylacrylamide)-integrated hydroxyapatite, Chem Commun (Camb) 16:1718–1719.CrossRefGoogle Scholar
  39. Shiokawa, T., Hattori, Y., Kawano, K., Ohguchi, Y., Kawakami, H., Toma, K., and Maitani, Y., 2005, Effect of polyethylene glycol linker chain length of folate-linked microemulsions loading aclacinomycin A on targeting ability and antitumor effect in vitro and in vivo, Clin Cancer Res 11:2018–2025.PubMedCrossRefGoogle Scholar
  40. Soni, S., Babbar, A. K., Sharma, R. K., and Maitra, A., 2006, Delivery of hydrophobised 5-fluorouracil derivative to brain tissue through intravenous route using surface modified nanogels, J Drug Target 14:87–95.PubMedCrossRefGoogle Scholar
  41. Soprano, D. R., Qin, P., and Soprano, K. J., 2004, Retinoic acid receptors and cancers, Annu Rev Nutr 24:201–221.PubMedCrossRefGoogle Scholar
  42. Standley, S. M., Mende, I., Goh, S. L., Kwon, Y. J., Beaudette, T. T., Engleman, E. G., and Frechet, J. M., 2007, Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines promotes antigen-specific CD8 T-cell immunity, Bioconjug Chem 18:77–83.PubMedCrossRefGoogle Scholar
  43. Tyagi, R., Lala, S., Verma, A. K., Nandy, A. K., Mahato, S. B., Maitra, A., and Basu, M. K., 2005, Targeted delivery of arjunglucoside I using surface hydrophilic and hydrophobic nanocarriers to combat experimental leishmaniasis, J Drug Target 13:161–171.PubMedCrossRefGoogle Scholar
  44. Varga, I., Szalai, I., Meszaros, R., and Gilanyi, T., 2006, Pulsating pH-responsive nanogels, J Phys Chem B Condens Matter Mater Surf Interfaces Biophys 110:20297–20301.PubMedGoogle Scholar
  45. Vinogradov, S. V., 2006, Colloidal microgels in drug delivery applications, Curr Pharm Des 12:4703–4712.PubMedCrossRefGoogle Scholar
  46. Vinogradov, S. V., Batrakova, E. V., and Kabanov, A. V., 1999, Poly(ethylene glycol)-polyethyleneimine NanoGel particles: novel drug delivery systems for antisense oligonucleotides, Colloids Surf B Biointerfaces 16:291–304.CrossRefGoogle Scholar
  47. Vinogradov, S. V., Bronich, T. K., and Kabanov, A. V., 2002, Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells, Adv Drug Deliv Rev 54:135–147.PubMedCrossRefGoogle Scholar
  48. Vinogradov, S. V., Batrakova, E. V., and Kabanov, A. V., 2004, Nanogels for oligonucleotide delivery to the brain, Bioconjug Chem 15:50–60.PubMedCrossRefGoogle Scholar
  49. Vinogradov, S. V., Zeman, A. D., Batrakova, E. V., and Kabanov, A. V., 2005, Polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs, J Control Release 107:143–157.PubMedCrossRefGoogle Scholar
  50. Vinogradov, S. V., Kohli, E., and Zeman, A. D., 2006, Comparison of nanogel drug carriers and their formulations with nucleoside 5’-triphosphates, Pharm Res 23:920–930.PubMedCrossRefGoogle Scholar
  51. Yan, M., Ge, J., Liu, Z., and Ouyang, P., 2006, Encapsulation of single enzyme in nanogel with enhanced biocatalytic activity and stability, J Am Chem Soc 128:11008–11009.PubMedCrossRefGoogle Scholar
  52. Yan, M., Liu, Z., Lu, D., and Liu, Z., 2007, Fabrication of single carbonic anhydrase nanogel against denaturation and aggregation at high temperature, Biomacromolecules 8:560–565.PubMedCrossRefGoogle Scholar
  53. Yu, S., Hu, J., Pan, X., Yao, P., and Jiang, M., 2006a, Stable and pH-sensitive nanogels prepared by self-assembly of chitosan and ovalbumin, Langmuir 22:2754–2759.PubMedCrossRefGoogle Scholar
  54. Yu, S., Yao, P., Jiang, M., and Zhang, G., 2006b, Nanogels prepared by self-assembly of oppositely charged globular proteins, Biopolymers 83:148–158.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Alexander V. Kabanov
    • 1
  • Serguei V. Vinogradov
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of Nebraska Medical CenterOmahaUSA

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