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.
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References
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.
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.
Bronich, T., Vinogradov, S., and Kabanov, A. V., 2001, Interaction of nanosized copolymer networks with oppositely charged amphiphilic molecules, Nano Lett 1:535–540.
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.
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.
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.
Daoud-Mahammed, S., Couvreur, P., and Gref, R., 2007, Novel self-assembling nanogels: stability and lyophilisation studies, Int J Pharm 332:185–191.
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.
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.
Galmarini, C. M., Mackey, J. R., and Dumontet, C., 2002, Nucleoside analogues and nucleobases in cancer treatment, Lancet Oncol 3:415–424.
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.
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.
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.
Hennink, W. E. and van Nostrum, C. F., 2002, Novel crosslinking methods to design hydrogels, Adv Drug Deliv Rev 54:13–36.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ricka, J. and Tanaka, T., 1984, Swelling of ionic gels: quantitative performance of the Donnan theory, Macromolecules 17:2916–2921.
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.
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.
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.
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.
Soprano, D. R., Qin, P., and Soprano, K. J., 2004, Retinoic acid receptors and cancers, Annu Rev Nutr 24:201–221.
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.
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.
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.
Vinogradov, S. V., 2006, Colloidal microgels in drug delivery applications, Curr Pharm Des 12:4703–4712.
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.
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.
Vinogradov, S. V., Batrakova, E. V., and Kabanov, A. V., 2004, Nanogels for oligonucleotide delivery to the brain, Bioconjug Chem 15:50–60.
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.
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.
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.
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.
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.
Yu, S., Yao, P., Jiang, M., and Zhang, G., 2006b, Nanogels prepared by self-assembly of oppositely charged globular proteins, Biopolymers 83:148–158.
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Kabanov, A.V., Vinogradov, S.V. (2008). Nanogels as Pharmaceutical Carriers. In: Torchilin, V. (eds) Multifunctional Pharmaceutical Nanocarriers. Fundamental Biomedical Technologies, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76554-9_3
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