Skip to main content
SpringerLink
Log in

Dendrimers in Drug Delivery

  • Chapter
  • First Online:
Book cover Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures

Abstract

Drugs are delivered by dendrimers by simple encapsulation, electrostatic interaction, or covalent conjugation. The application of dendrimer–drug conjugates by oral, intravenous, intraperitoneal, intratumoral, transdermal, ocular, etc. administration is discussed. Drug–dendrimer conjugates have two advantages over drug–dendrimer complexes and traditional drug dosing: prolonged lifetime and more stable level of the active substance. Many examples of different dendrimeric structures are given together with examples of their application in drug delivery. Dendrimers are also supposed to become an important tool for tissue-specific drug targeting. The topics of drug delivery, dendrimer solubility (both dendrimers as such and their influence to drug solubility), dendrimer toxicity and biocompatibility, are closely related and influence each other, therefore see also Chaps. 10 and 11.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agrawal, P., Gupta, U., Jain, N.: Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery of chloroquine phosphate. Biomater. 28(22), 3349–3359 (2007)

    Article  CAS  Google Scholar 

  2. Astruc, D., Boisselier, E., Ornelas, C.: Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. Chem. Rev. 110(4), 1857–1959 (2010)

    Article  PubMed  CAS  Google Scholar 

  3. Bagalkot, V., Lee, I.H., Yu, M.K., Lee, E., Park, S., Lee, J.H., Jon, S.: A combined chemoimmunotherapy approach using a plasmid–doxorubicin complex. Mol. Pharmaceut. 6(3), 1019–1028 (2009)

    Article  CAS  Google Scholar 

  4. Balogh, L.: Dendrimer 101. Adv. Exp. Med. Biol. 620, 136–155 (2007)

    Article  PubMed  Google Scholar 

  5. Bhadra, D., Yadav, A., Bhadra, S., Jain, N.: Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting. Int. J. Pharmaceut. 295(1–2), 221–233 (2005)

    Article  CAS  Google Scholar 

  6. Biricova, V., Laznickova, A.: Dendrimers: analytical characterization and applications. Bioorg. Chem. 37(6), 185–192 (2009)

    Article  PubMed  CAS  Google Scholar 

  7. Chabre, Y.M., Brisebois, P.P., Abbassi, L., Kerr, S.C., Fahy, J.V., Marcotte, I., Roy, R.: Hexaphenylbenzene as a rigid template for the straightforward syntheses of “star-shaped” glycodendrimers. J. Org. Chem. 76(2), 724–727 (2011)

    Article  PubMed  CAS  Google Scholar 

  8. Cheng, Y., Gao, Y., Rao, T., Li, Y., Xu, T.: Dendrimer-based prodrugs: design, synthesis, screening and biological evaluation. Comb. Chem. High Through Screen. 10(5), 336–349 (2007)

    Article  CAS  Google Scholar 

  9. Cheng, Y., Wang, J., Rao, T., He, X., Xu, T.: Pharmaceutical applications of dendrimers: Promising nanocarriers for drug delivery. Front Biosci 13(4), 1447–1471 (2008)

    Article  PubMed  CAS  Google Scholar 

  10. Cheng, Y., Xu, T.: The effect of dendrimers on the pharmacodynamic and pharmacokinetic behaviors of non-covalently or covalently attached drugs. Eur. J. Med. Chem. 43(11), 2291–2297 (2008)

    Article  PubMed  CAS  Google Scholar 

  11. Cheng, Y., Xu, Z., Ma, M., Xu, T.: Dendrimers as drug carriers: applications in different routes of drug administration. J. Pharm. Sci. 97(1), 123–143 (2008)

    Article  PubMed  CAS  Google Scholar 

  12. Choi, Y., Baker Jr., J.: Targeting cancer cells with DNA-assembled dendrimers: a mix and match strategy for cancer. Cell Cycl. 4(5), 669–671 (2005)

    Article  CAS  Google Scholar 

  13. Dai, X.H., Zhang, H.D., Dong, C.M.: Fabrication, biomolecular binding, in vitro drug release behavior of sugar-installed nanoparticles from star poly(\(\epsilon \)-caprolactone)/glycopolymer biohybrid with a dendrimer core. Polymer. 50(19), 4626–4634 (2009)

    Article  CAS  Google Scholar 

  14. Darbre, T., Reymond, J.L.: Peptide dendrimers as artificial enzymes, receptors, and drug-delivery agents. Acc. Chem. Res. 39(12), 925–934 (2006)

    Article  PubMed  CAS  Google Scholar 

  15. Falciani, C., Lelli, B., Brunetti, J., Pileri, S., Cappelli, A., Pini, A., Pagliuca, C., Ravenni, N., Bencini, L., Menichetti, S., Moretti, R., De Prizio, M., Scatizzi, M., Bracci, L.: Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept. Curr. Cancer Drug Targets 10(7), 695–704 (2010)

    Article  PubMed  CAS  Google Scholar 

  16. Fox, M., Szoka, F., Frechet, J.: Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. Acc. Chem. Res. 42(8), 1141–1151 (2009)

    Article  PubMed  CAS  Google Scholar 

  17. Gillies, E., Frechet, J.: Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 10(1), 35–43 (2005)

    Article  PubMed  CAS  Google Scholar 

  18. Gu, Z., Luo, K., She, W., Wu, Y., He, B.: New-generation biomedical materials: peptide dendrimers and their application in biomedicine. Sci. China. Chem. 53, 458–478 (2010)

    Article  CAS  Google Scholar 

  19. Guo, B., Sun, X., Zhou, Y., Yan, D.: Supramolecular self-assembly and controllable drug release of thermosensitive hyperbranched multiarm copolymers. Sci. China. Chem. 53, 487–494 (2010)

    Article  CAS  Google Scholar 

  20. Guo, R., Wang, H., Peng, C., Shen, M., Zheng, L., Zhang, G., Shi, X.: Enhanced X-ray attenuation property of dendrimer-entrapped gold nanoparticles complexed with diatrizoic acid. J. Mater. Chem. 21(13), 5120–5127 (2011)

    Article  CAS  Google Scholar 

  21. Hamilton, S., Harth, E.: Molecular dendritic transporter nanoparticle vectors provide efficient intracellular delivery of peptides. ACS Nano. 3(2), 402–410 (2009)

    Article  PubMed  CAS  Google Scholar 

  22. Hu, J., Xu, T., Cheng, Y.: NMR insights into dendrimer-based host–guest systems. Chem. Rev. (in press). doi: 10.1021/cr200333h

    Google Scholar 

  23. Inapagolla, R., Guru, B.R., Kurtoglu, Y.E., Gao, X., Lieh-Lai, M., Bassett, D.J.P., Kannan, R.M.: In vivo efficacy of dendrimer-methylprednisolone conjugate formulation for the treatment of lung inflammation. Int. J. Pharmaceut. 399(1–2), 140–147 (2010)

    Article  CAS  Google Scholar 

  24. Jain, A., Agarwal, A., Majumder, S., Lariya, N., Khaya, A., Agrawal, H., Majumdar, S., Agrawal, G.P.: Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug. J. Control Rel. 148(3), 359–367 (2010)

    Article  CAS  Google Scholar 

  25. Janib, S.M., Moses, A.S., MacKay, J.A.: Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev. 62(11), 1052–1063 (2010)

    Article  PubMed  CAS  Google Scholar 

  26. Ke, W., Zhao, Y., Huang, R., Jiang, C., Pei, Y.: Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system. J. Pharm. Sci. 97(6), 2208–2216 (2008)

    Article  PubMed  CAS  Google Scholar 

  27. Kim, H.Y., Sohn, J., Wijewickrama, G.T., Edirisinghe, P., Gherezghiher, T., Hemachandra, M., Lu, P.Y., Chandrasena, R.E., Molloy, M.E., Tonetti, D.A., Thatcher, G.R.: Click synthesis of estradiol–cyclodextrin conjugates as cell compartment selective estrogens. Bioorg. Med. Chem. 18(2), 809–821 (2010)

    Article  PubMed  CAS  Google Scholar 

  28. Kojima, C., Regino, C., Umeda, Y., Kobayashi, H., Kono, K.: Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers. Int. J. Pharmaceut. 383(1–2), 293–296 (2010)

    Article  CAS  Google Scholar 

  29. Lagnoux, D., Darbre, T., Schmitz, M., Reymond, J.L.: Inhibition of mitosis by glycopeptide dendrimer conjugates of colchicine. Chem. Eur. J. 11(13), 3941–3950 (2005)

    Article  PubMed  CAS  Google Scholar 

  30. Larson, N., Ghandehari, H.: Polymeric conjugates for drug delivery. Chem. Mater. 24(5), 840–853 (2012)

    Article  PubMed  CAS  Google Scholar 

  31. Lee, I.H., An, S., Yu, M.K., Kwon, H.K., Im, S.H., Jon, S.: Targeted chemoimmunotherapy using drug-loaded aptamer–dendrimer bioconjugates. J. Control Rel. 155(3), 435–441 (2011)

    Article  CAS  Google Scholar 

  32. Li, J., Loh, X.: Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv. Drug Deliv. Rev. 60(9), 1000–1017 (2008)

    Article  PubMed  CAS  Google Scholar 

  33. Li, Y., Dong, H., Wang, K., Shi, D., Zhang, X., Zhuo, R.: Stimulus-responsive polymeric nanoparticles for biomedical applications. Sci. China. Chem. 53, 447–457 (2010)

    Article  Google Scholar 

  34. Li, X., Zhang, C., Le Guyader, L., Chen, C.: “Smart” nanomaterials for cancer therapy. Sci. China. Chem. 53, 2241–2249 (2010)

    Article  CAS  Google Scholar 

  35. Maiti, K., Jeon, O.Y., Lee, W., Chung, S.K.: Design, synthesis, and delivery properties of novel guanidine-containing molecular transporters built on dimeric inositol scaffolds. Chem. Eur. J. 13(3), 762–775 (2007)

    Article  PubMed  CAS  Google Scholar 

  36. Martini, G., Ciani, L.: Electron spin resonance spectroscopy in drug delivery. Phys. Chem. Chem. Phys. 11(2), 211–254 (2009)

    Article  PubMed  CAS  Google Scholar 

  37. McNerny, D.Q., Kukowska-Latallo, J.F., Mullen, D.G., Wallace, J.M., Desai, A.M., Shukla, R., Huang, B., Banaszak Holl, M.M., Baker, J.R.: RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies. Bioconjug. Chem. 20(10), 1853–1859 (2009)

    Article  PubMed  CAS  Google Scholar 

  38. Medina, S., Tekumalla, V., Chevliakov, M., Shewach, D., Ensminger, W., El-Sayed, M.: N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers. Biomater. 32(17), 4118–4129 (2011)

    Article  CAS  Google Scholar 

  39. Menjoge, A.R., Kannan, R.M., Tomalia, D.A.: Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov. Today 15(5–6), 171–185 (2010)

    Article  PubMed  CAS  Google Scholar 

  40. Menjoge, A.R., Rinderknecht, A.L., Navath, R.S., Faridnia, M., Kim, C.J., Romero, R., Miller, R.K., Kannan, R.M.: Transfer of PAMAM dendrimers across human placenta: Prospects of its use as drug carrier during pregnancy. J. Control Rel. 150(3), 326 – 338 (2011)

    Article  CAS  Google Scholar 

  41. Mochizuki, S., Sakurai, K.: A novel polysaccharide/polynucleotide complex and its application to bio-functional DNA delivery system. Polym. J. 41(5), 343–353 (2009)

    Article  CAS  Google Scholar 

  42. Muthu, M., Singh, S.: Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders. Nanomedicine 4(1), 105–118 (2009)

    CAS  Google Scholar 

  43. Nelson, A., Stoddart, J.: Dynamic multivalent lactosides displayed on cyclodextrin beads dangling from polymer strings. Org. Lett. 5(21), 3783–3786 (2003)

    Article  PubMed  CAS  Google Scholar 

  44. Ouyang, L., Pan, J., Zhang, Y., Guo, L.: Synthesis of second-and third-generation Asp oligopeptide conjugated dendrimers for bone-targeting drug delivery. Synth. Commun. 39(22), 4039–4052 (2009)

    Article  CAS  Google Scholar 

  45. Pang, Y., Liu, J., Su, Y., Zhu, B., Huang, W., Zhou, Y., Zhu, X., Yan, D.: Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release. Sci. China. Chem. 53, 2497–2508 (2010)

    Article  CAS  Google Scholar 

  46. Patri, A., Kukowska-Latallo, J., Baker Jr., J.: Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv. Drug Deliv. Rev. 57(15), 2203–2214 (2005)

    Article  PubMed  CAS  Google Scholar 

  47. Prajapati, R., Tekade, R., Gupta, U., Gajbhiye, V., Jain, N.: Dendimer-mediated solubilization, formulation development and in vitro-in vivo assessment of piroxicam. Mol. Pharmaceut. 6(3), 940–950 (2009)

    Article  CAS  Google Scholar 

  48. Prieto, M., Bacigalupe, D., Pardini, O., Amalvy, J., Venturini, C., Morilla, M., Romero, E.: Nanomolar cationic dendrimeric sulfadiazine as potential antitoxoplasmic agent. Int. J. Pharmaceut. 326(1–2), 160–168 (2006)

    Article  CAS  Google Scholar 

  49. Reul, R., Renette, T., Bege, N., Kissel, T.: Nanoparticles for paclitaxel delivery: a comparative study of different types of dendritic polyesters and their degradation behavior. Int. J. Pharmaceut. 407(1–2), 190–196 (2011)

    Article  CAS  Google Scholar 

  50. Rolland, O., Turrin, C.O., Caminade, A.M., Majoral, J.P.: Dendrimers and nanomedicine: multivalency in action. New J. Chem. 33(9), 1809–1824 (2009)

    Article  CAS  Google Scholar 

  51. Rosen, B., Wilson, C., Wilson, D., Peterca, M., Imam, M., Percec, V.: Dendron-mediated self-assembly, disassembly, and self-organization of complex systems. Chem. Rev. 109(11), 6275–6540 (2009)

    Article  PubMed  CAS  Google Scholar 

  52. Samad, A., Alam, M., Saxena, K.: Dendrimers: a class of polymers in the nanotechnology for the delivery of active pharmaceuticals. Curr. Pharm. Des. 15(25), 2958–2969 (2009)

    Article  PubMed  CAS  Google Scholar 

  53. Sebestik, J., Niederhafner, P., Jezek, J.: Peptide and glycopeptide dendrimers and analogous dendrimeric structures and their biomedical applications. Amino Acids 40(2), 301–370 (2011)

    Article  PubMed  CAS  Google Scholar 

  54. Shi, Y., Porter, W., Merdan, T., Li, L.: Recent advances in intravenous delivery of poorly water-soluble compounds. Expert Opin. Drug Deliv. 6(12), 1261–1282 (2009)

    Article  PubMed  CAS  Google Scholar 

  55. Sosnik, A., Chiappetta, D.A., Carcaboso, A.M.: Drug delivery systems in HIV pharmacotherapy: what has been done and the challenges standing ahead. J. Control Rel. 138(1), 2–15 (2009)

    Article  CAS  Google Scholar 

  56. Suriano, F., Pratt, R., Tan, J.P.K., Wiradharma, N., Nelson, A., Yang, Y.Y., Dubois, P., Hedrick, J.L.: Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery. Biomater. 31(9), 2637–2645 (2010)

    Article  CAS  Google Scholar 

  57. Svenson, S.: Dendrimers as versatile platform in drug delivery applications. Eur. J. Pharm. Biopharm. 71(3), 445–462 (2009)

    Article  PubMed  CAS  Google Scholar 

  58. Svenson, S., Chauhan, A.: Dendrimers for enhanced drug solubilization. Nanomedicine 3(5), 679–702 (2008)

    Article  PubMed  CAS  Google Scholar 

  59. Svenson, S., Tomalia, D.A.: Nanoparticulates as Drug Carriers. Dendrimers as Nanoparticular Drug Carriers, pp. 277–306. Imperial College Press, London (2006)

    Google Scholar 

  60. Theodossiou, T., Pantos, A., Tsogas, I., Paleos, C.: Guanidinylated dendritic molecular transporters: prospective drug delivery systems and application in cell transfection. ChemMedChem 3(11), 1635–1643 (2008)

    Article  PubMed  CAS  Google Scholar 

  61. Thomas, T., Shukla, R., Kotlyar, A., Kukowska-Latallo, J., Baker Jr., J.: Dendrimer-based tumor cell targeting of fibroblast growth factor-1. Bioorg. Med. Chem. Lett. 20(2), 700–703 (2010)

    Article  PubMed  CAS  Google Scholar 

  62. Tong, R., Cheng, J.: Anticancer polymeric nanomedicines. Polym. Rev. 47(3), 345–381 (2007)

    Article  CAS  Google Scholar 

  63. Xiao, C., Tian, H., Zhuang, X., Chen, X., Jing, X.: Recent developments in intelligent biomedical polymers. Sci. China. B 52, 117–130 (2009)

    Article  CAS  Google Scholar 

  64. Xu, X., Li, C., Li, H., Liu, R., Jiang, C., Wu, Y., He, B., Gu, Z.: Polypeptide dendrimers: self-assembly and drug delivery. Sci. China. Chem. 54, 326–333 (2011)

    Article  CAS  Google Scholar 

  65. Yang, C., Li, H., Wang, X., Li, J.: Cationic supramolecules consisting of oligoethylenimine-grafted α-cyclodextrins threaded on poly(ethylene oxide) for gene delivery. J. Biomed. Mater. Res. A 89(1), 13–23 (2009)

    PubMed  Google Scholar 

  66. Yellepeddi, V., Kumar, A., Palakurthi, S.: Surface modified poly(amido) amine dendrimers as diverse nanomolecules for biomedical applications. Expert Opin. Drug Deliv. 6(8), 835–850 (2009)

    Article  PubMed  CAS  Google Scholar 

  67. Yellepeddi, V.K., Kumar, A., Maher, D.M., Chauhan, S.C., Vangara, K.K., Palakurthi, S.: Biotinylated PAMAM dendrimers for intracellular delivery of cisplatin to ovarian cancer: role of SMVT. Anticancer Res. 31(3), 897–906 (2011)

    PubMed  CAS  Google Scholar 

  68. Yoon, H.J., Jang, W.D.: Polymeric supramolecular systems for drug delivery. J. Mater. Chem. 20(2), 211–222 (2010)

    Article  CAS  Google Scholar 

  69. Zhou, Y., Guo, Z., Zhang, Y., Huang, W., Zhou, Y., Yan, D.: Hyperbranched polyamidoamines containing β-cyclodextrin for controlled release of chlorambucil. Macromol. Biosci. 9(11), 1090–1097 (2009)

    Article  PubMed  CAS  Google Scholar 

  70. Zhu, S., Hong, M., Zhang, L., Tang, G., Jiang, Y., Pei, Y.: PEGylated PAMAM dendrimer-doxorubicin conjugates: In vitro evaluation and in vivo tumor accumulation. Pharmaceut. Res. 27(1), 161–174 (2010)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Spectroscopy, Institute of Organic Chemistry and Biochemistry, AS CR, vvi, Prague, Czech Republic

    Jaroslav Šebestík

  2. Institute of Molecular Genetics AS CR, vvi, Prague, Czech Republic

    Milan Reiniš

  3. Laboratory of Glycoconjugates, Institute of Organic Chemistry and Biochemistry, AS CR, vvi, Prague, Czech Republic

    Jan Ježek

Authors
  1. Jaroslav Šebestík
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milan Reiniš
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Ježek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Šebestík, J., Reiniš, M., Ježek, J. (2012). Dendrimers in Drug Delivery. In: Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1206-9_13

Download citation

Publish with us

Policies and ethics

Search

Navigation