PAMAM Dendrimers as Nanoscale Oral Drug Delivery Systems

  • Kelly M. Kitchens
  • Hamidreza Ghandehari
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume X)


The application of nanotechnology to the diagnosis and treatment of diseases has coined the term nanomedicine. Nanometer-scale biomaterials have their role in nanomedicine since their nanoscopic size allows interaction with cellular membranes, subcellular organelles, passage through the microvasculature, and may reduce immunogenicity by avoiding reticuloendothelial uptake. Such features are desirable for nanomaterials to enhance the residence of poorly bioavailable drugs in the systemic circulation. Nanomaterials used as drug delivery systems, also termed nanocarriers, should be freely permeable to tumor vasculature since the endothelial pores range from 100 to 1000 nm (Hobbs et al., 1998). On the other hand, several moieties can be incorporated in these nanocarriers to enhance the delivery of bioactive and diagnostic agents. These include imaging agents for detection of the nanocarriers in the body, targeting ligands to direct the carrier to the site of action, enhanced...


Surface Group PAMAM Dendrimers Carbosilane Dendrimers Extravasation Time Cationic Dendrimers 
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.



Full name:


p-Isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid






Biomolecular Research Institute


Chloramphenicol acetyl-transferase


Computed topography








Deoxyribonucleic acid


Diethylenetriaminepentaacetic acid


Early endosomal antigen 1


Fluorescein isothiocyanate








Herpes simplex virus type 2


Injected dose per gram




Lysosome-associated membrane protein 1


Lactate dehydrogenase


Matrix-assisted laser desorption ionization time of flight


Madin–Darby canine kidney


Magnetic resonance imaging


3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide


Nuclear magnetic resonance


Apparent permeability


Polyacrylamide gel electrophoresis




Poly(ethylene glycol)




Poly(ethylene oxide)






Poly(vinyl alcohol)


Small-angle neutron scattering


Small-angle X-ray scattering


Sodium dodecyl sulfate


Transepithelial electrical resistance


Transmission electron microscopy


Tumor necrosis factor



Financial support was in part provided by the National Institute of General Medical Sciences National Research Service Award predoctoral fellowship to Kelly Kitchens (F31-GM67278) and a grant from the National Institutes of Health (RO1EB007470).


  1. Adamson, R. H., & Clough, G. (1992). Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. J Physiol, 445, 473–486.PubMedGoogle Scholar
  2. Artursson, P. (1990). Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J Pharm Sci, 79(6), 476–482.PubMedGoogle Scholar
  3. Aulenta, F., Drew, M. G., Foster, A., Hayes, W., Rannard, S., Thornthwaite. D. W., Worrall, D. R., Youngs, T. G. (2005). Synthesis and characterization of fluorescent poly (aromatic amide) dendrimers. J Org Chem, 70(1), 63–78.PubMedGoogle Scholar
  4. Aungst, B. J. (2000). Intestinal permeation enhancers. J Pharm Sci, 89(4), 429–442.PubMedGoogle Scholar
  5. Bayele, H. K., Ramaswamy, C., Wilderspin, A. F., Srai, K. S., Toth, I., & Florence, A. T. (2006). Protein transduction by lipidic peptide dendrimers. J Pharm Sci, 95(6), 1227–1237.PubMedGoogle Scholar
  6. Behr, J. P. (1994). Gene transfer with synthetic cationic amphiphiles: Prospects for gene therapy. Bionconjug Chem, 5(5), 382–389.Google Scholar
  7. Bielinska, A., Kukowska-Latallo, J. F., Johnson, J., Tomalia, D. A., & Baker, J. R., Jr. (1996). Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using starburst PAMAM dendrimers. Nucleic Acids Res, 24(11), 2176–2182.PubMedGoogle Scholar
  8. Boas, U, Karlsson, A. J., de Waal, B. F., Meijer, E. W. (2001). Synthesis and properties of new thiourea-functionalized poly (propylene imine) dendrimers and their role as hosts for urea functionalized guests. J Org Chem, 66(6), 2136–2145.PubMedGoogle Scholar
  9. Bourne, N. (2000). Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother, 44(9), 2471–2474.PubMedGoogle Scholar
  10. Brauge, L., Magro, G., Caminade, A. M., & Majoral, J. P. (2001). First divergent strategy using two AB(2) unprotected monomers for the rapid synthesis of dendrimers. J Am Chem Soc, 123(27), 6698–6699.PubMedGoogle Scholar
  11. Brothers II, H. M., Piehler, I. T., & Tomalia, D. A. (1998). Slab-gel and capillary electrophoretic characterization of polyamidoamine dendrimers. J Chromatogr A, 814(1–2), 233–246.Google Scholar
  12. Caminade, A. M., Laurent, R., & Majoral, J. P. (2005). Characterization of dendrimers. Adv Drug Del Rev, 57(15), 2130–2146.Google Scholar
  13. Chai, M., Niu, Y., Youngs, W. J., Rinaldi, P.L. (2001). Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques. J Am Chem Soc, 123(20), 4670–4678.PubMedGoogle Scholar
  14. Chai, M., Pi, Z., Tessier, C., & Rinaldi, P. L. (1999). Preparation of carbosilane dendrimers and their characterization using 1H/13C/29Si triple resonance 3D NMR methods. J Am Chem Soc, 121(2), 273–279.Google Scholar
  15. Chauhan, A. S., Sridevi, S., Chalasani, K. B., Jain, A. K., Jain, S. K., & Jain, N. K. (2003). Dendrimer-mediated transdermal delivery: Enhanced bioavailability of indomethacin. J Control Release, 90(3), 335–343.PubMedGoogle Scholar
  16. Chen, H. T., Neerman, M. F., Parrish, A. R., & Simanek, E. E. (2004). Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. J Am Chem Soc, 126, 10044–10048.PubMedGoogle Scholar
  17. Choe, Y. H., Conover, C. D., Wu, D., Royzen, M., Gervacio, Y., & Borowski, V. (2002). Anticancer drug delivery systems: Multi-loaded N4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors. J Control Release, 79(1–3), 55–70.PubMedGoogle Scholar
  18. Choi, Y. S., Thomas, T., Kotlayr, A., Islam, M. T., & Baker, J. R. (2005). Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. Chem Biol, 12(1), 35–43.PubMedGoogle Scholar
  19. Cloninger, M. J. (2002). Biological applications of dendrimers. Curr Opin Chem Biol, 6(6), 742–748.PubMedGoogle Scholar
  20. D'Emanuele, A., & Attwood, D. (2005). Dendrimer-drug interactions. Adv Drug Deliv Rev, 57(15), 2147–2162.PubMedGoogle Scholar
  21. D'Emanuele, A., Jevprasesphant, R., Penny, J., & Attwood, D. (2004). The use of a dendrimer-propranolol prodrug to bypass efflux transporters and enhance oral bioavailability. J Control Release, 95(3), 447–453.PubMedGoogle Scholar
  22. DeLong, R., Stephenson, K., Loftus, T., Fisher, M., Alahari, S., Nolting, A., & Juliano, R. L. (1997). Characterization of complexes of oligonucleotides with polyamidoamine starburst dendrimers and effects on intracellular delivery. J Pharm Sci, 86(6), 762–764.PubMedGoogle Scholar
  23. Dufes, C., Keith, W. N., Bilsland, A., Proutski, I., Uchegbu, I. F., & Schatzlein, A. G. (2005a). Synthetic anticancer gene medicine exploits intrinsic antitumor activity of cationic vector to cure established tumors. Cancer Res, 65(18), 8079–8084.Google Scholar
  24. Dufes, C., Uchegbu, I. F., & Schatzlein, A. G. (2005b). Dendrimers in gene delivery. Adv Drug Deliv Rev, 57(15), 2177–2202.Google Scholar
  25. Duncan, R., & Izzo, L. (2005). Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev, 57(15), 2215–2237.PubMedGoogle Scholar
  26. Duncan, R., & Spreafico, F. (1994). Polymer conjugates. Pharmacokinetic considerations for design and development. Clin Pharmacokinet, 27(4), 290–306.PubMedGoogle Scholar
  27. Dunphy, I., Vinogradov, S. A., & Wilson, D. F. (2002). Oxyphor R2 and G2: Phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. Anal Biochem, 310(2), 191–198.PubMedGoogle Scholar
  28. El-Sayed, M., Ginski, M., Rhodes, C., & Ghandehari, H. (2002). Transepithelial transport of poly(amidoamine) dendrimers across Caco–2 cell monolayers. J Control Release, 81(3), 355–365.PubMedGoogle Scholar
  29. El-Sayed, M., Ginski, M., Rhodes, C., & Ghandehari, H. (2003a). Influence of surface chemistry of poly (amidoamine) dendrimers on Caco-2 cell monolayers. J Bioactive Compat Poly, 18, 7–22.Google Scholar
  30. El-Sayed, M., Rhodes, C. A., Ginski, M., & Ghandehari, H. (2003b). Transport mechanism(s) of poly (amidoamine) dendrimers across Caco-2 cell monolayers. Int J Pharm, 265(1–2), 151–157.Google Scholar
  31. El-Sayed, M., Kiani, M. F., Naimark, M. D., Hikal, A. H., & Ghandehari, H. (2001). Extravasation of poly(amidoamine) (PAMAM) dendrimers across microvascular network endothelium. Pharm Res, 18(1), 23–28.PubMedGoogle Scholar
  32. Esfand, R., & Tomalia, D. A. (2001). Poly (amidoamine) (PAMAM) dendrimers: From biomimicry to drug delivery and biomedical applications. Drug Discov Today, 6(8), 427–436.PubMedGoogle Scholar
  33. Felder, T., Schalley, C. A., Fakhrnabavi, H., & Lukin, O. (2005). A combined ESI- and MALDI-MS(/MS) study of peripherally persulfonylated dendrimers: False negative results by MALDI-MS and analysis of defects. Chemistry, 11(19), 5625–5636.PubMedGoogle Scholar
  34. Fischer, D., Li, Y., Ahlemeyer, B., Krieglstein, J., & Kissel, T. (2003). In vitro cytotoxicity testing of polycations: Influence of polymer structure on cell viability and hemolysis. Biomaterials, 24(7), 1121–1131.PubMedGoogle Scholar
  35. Florence, A. T. (1997). The oral absorption of micro- and nanoparticles: Neither exceptional nor unusual. Pharm Res, 14, 259–266.PubMedGoogle Scholar
  36. Florence, A. T., Sakthivel, T., & Toth, I. (2000). Oral uptake and translocation of a polylysine dendrimer with a lipid surface. J Control Release, 65(1–2), 253–259.PubMedGoogle Scholar
  37. Fu, Y., Nitecki, D. E., Maltby, D., Simon, G. H., Berejnoi, K., Raatschen, H. J., Yeh, B. M., Shames, D. M., & Brasch, R. C. (2006). Dendritic iodinated contrast agents with PEG-cores for CT imaging: Synthesis and preliminary characterization. Bioconjug Chem, 17(4), 1043–1056.PubMedGoogle Scholar
  38. Grinstaff, M. W. (2002). Biodendrimers: New polymeric biomaterials for tissue engineering. Chemistry, 8(13), 2838–2846.Google Scholar
  39. Haensler, J., & Szoka, F.C., Jr. (1993). Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bionconjug Chem, 4(5), 372–379.Google Scholar
  40. Halford, B. (2005). Dendrimers branch out. Chem Eng News, 83, 30–36.Google Scholar
  41. Hawker, C. J., & Frechet, J. M. J. (1990). Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules. J Am Chem Soc, 112(21), 7638–7647.Google Scholar
  42. Hilgers, A. R., Conradi, R. A., & Burton, P. S. (1990). Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm Res, 7(9), 902–910.PubMedGoogle Scholar
  43. Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Griffith, L., Torchilin, V. P., Jain, & R. K. (1998). Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proc Natl Acad Sci USA, 95(8), 4607–4612.Google Scholar
  44. Hong, M. Y., Kim, Y. J., Lee, J. W., Kim, K., Lee, J. H., Yoo, J. S., Bae, S. H., Choi, B. S., & Kim, H. S. (2004a). Synthesis and characterization of tri(ethylene oxide)-attached poly(amidoamine) dendrimer layers on gold. J Colloid Interface Sci, 274(1), 41–48.Google Scholar
  45. Hong, S., Leroueil, P. R., Janus, E. K., Peters, J. L., Kober, M. M., Islam, M. T., Orr, B. G. Baker, J. R., Jr., & Banaszak Holl, M. M. (2006). Interaction of polycationic polymers with supported lipid bilayers and cells: Nanoscale hole formation and enhanced membrane permeability. Bioconjug Chem, 17(3), 728–734.PubMedGoogle Scholar
  46. Hong, S., Bielinska, A. U., Mecke, A., Keszler, B., Beals, J. L., Shi, X., Balogh, L., Orr, B. G., Baker, J. R., Jr., & Banaszak Holl, M. M (2004b). Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: Hole formation and the relation to transport. Bioconjug Chem, 15(4), 774–782.Google Scholar
  47. Huang, Q. R., Dubin, P. L., Lal, J., Moorefield, C. N., & Newkome, G. R. (2005). Small-angle neutron scattering studies of charged carboxyl-terminated dendrimers in solutions. Langmuir, 21(7), 2737–2742.PubMedGoogle Scholar
  48. Hughes, J. A., Aronsohn, A. I., Avrutskaya, A. V., & Juliano, R. L. (1996). Evaluation of adjuvants that enhance the effectiveness of antisense oligodeoxynucleotides. Pharm Res, 13(3), 404–410.PubMedGoogle Scholar
  49. Hummelen, J. C., Van Dongen, J. L. J., & Meijer, E. W. (1997). Electrospray mass spectrometry of poly(propylene imine) dendrimers – the issue of dendritic purity or polydispersity. Chem Eur J, 3(9), 1489–1493.Google Scholar
  50. Ihre, H. R., Padilla De Jesus, O. L., Szoka, F. C., Jr., & Frechet, J. M. (2002). Polyester dendritic systems for drug delivery applications: Design, synthesis, and characterization. Bioconjug Chem, 13(3), 443–452.PubMedGoogle Scholar
  51. Irvine, J. D., Takahashi, L., Lockhart, K., Cheong, J., Tolan, J. W., Selick, H. E., & Grove, J. R. (1999). MDCK (Madin-Darby Canine Kidney) cells: A tool for membrane permeability screening. J Pharm Sci, 88(1), 28–33.PubMedGoogle Scholar
  52. Jackson, C. L., Chanzy, H. D., Booy, F. P., Drake, B. J., Tomalia, D. A., Bauer, B. J., & Amis, E. J. (1998). Visualization of dendrimer molecules by transmission electron microscopy (TEM): Staining methods and cryo-TEM of vitrified solutions. Macromolecules, 31(18), 6259–6265.Google Scholar
  53. Jevprasesphant, R., Penny, J., Attwood, D., & D'Emanuele, A. (2004). Transport of dendrimer nanocarriers through epithelial cells via the transcellular route. J Control Release, 97(2), 259–267.PubMedGoogle Scholar
  54. Jevprasesphant, R., Penny, J., Attwood, D., McKeown, N. B., & D'Emanuele, A. (2003a). Engineering of dendrimer surfaces to enhance transepithelial transport and reduce cytotoxicity. Pharm Res, 20(10), 1543–1550.Google Scholar
  55. Jevprasesphant, R., Penny, J., Jalal, R., Attwood, D., McKeown, N. B., & D'Emanuele, A. (2003b). The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm, 252(1–2), 263–266.Google Scholar
  56. Jiang, Y. H., Emau, P., Cairns, J. S., Flanary, L., Morton, W. R., McCarthy, T. D., & Tsai, C.C. (2005). SPL7013 gel as a topical microbicide for prevention of vaginal transmission of SHIV89.6p in macaques. AIDS Res Hum Retroviruses, 21(3), 207–213.PubMedGoogle Scholar
  57. Juliano, R. L. (2006). Intracellular delivery of oligonucleotide conjugates and dendrimer complexes. Ann NY Acad Sci, 1082, 18–26.PubMedGoogle Scholar
  58. Kang, H., DeLong, R., Fisher, M. H., & Juliano, R. L. (2005). Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm Res(12), 22, 2099–2106.PubMedGoogle Scholar
  59. Kannan, S., Kolhe, P., Raykova, V., Glibatec, M., Kannan, R. M., Lieh-Lai, M., & Bassett, D. (2004). Dynamics of cellular entry and drug delivery by dendritic polymers into human lung epithelial carcinoma cells. J Biomater Sci Polym Ed, 15(3), 311–330.PubMedGoogle Scholar
  60. Karoonuthaisiri, N., Titiyevskiy, K., & Thomas, J. L. (2003). Destabilization of fatty acid-containing liposomes by polyamidoamine dendrimers. Colloids Surf B Biointerfaces, 27(24), 365–375.Google Scholar
  61. Khandare, J., Kolhe, P., Pillai, O., Kannan, S., Lieh-Lai, M., & Kannan, R. M. (2005). Synthesis, cellular transport, and activity of polyamidoamine dendrimer-methylprednisolone conjugates. Bioconjug Chem, 16(2), 330–337.PubMedGoogle Scholar
  62. Kim, T. I., Seo, H. J., Choi, J. S., Jang, H. S., Baek, J. U., Kim, K., & Park, J. S. (2004). PAMAM-PEG-PAMAM: Novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules, 5(6), 2487–2492.PubMedGoogle Scholar
  63. Kitchens, K. M., El-Sayed, M. E., & Ghandehari, H. (2005). Transepithelial and endothelial transport of poly (amidoamine) dendrimers. Adv Drug Deliv Rev, 57(15), 2163–2176.PubMedGoogle Scholar
  64. Kitchens, K. M., Foraker, A. B., Kolhatkar, R. B., Swaan, P. W., & Ghandehari, H. (2007). Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells. Pharamaceutical Research, 24:2138–2145.Google Scholar
  65. Kitchens, K. M., Kolhatkar, R. B., Swaan, P. W., Eddington, N. D., & Ghandehari, H. (2006). Transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers: Influence of size, charge and fluorescent labeling. Pharm Res, 23(12), 2818–2826.PubMedGoogle Scholar
  66. Kobayashi, H., & Brechbiel, M. W. (2005). Nano-sized MRI contrast agents with dendrimer cores. Adv Drug Deliv Rev, 57(15), 2271–2286.PubMedGoogle Scholar
  67. Kobayashi, H., Kawamoto, S., Saga, T., Sato, N., Hiraga, A., Ishimori, T., Konishi, J., Togashi, K., & Brechbiel, M. W. (2001a). Positive effects of polyethylene glycol conjugation to generation-4 polyamidoamine dendrimers as macromolecular MR contrast agents. Magn Reson Med, 46(4), 781–788.Google Scholar
  68. Kobayashi, H., Sato, N., Kawamoto, S., Saga, T., Hiraga, A., Haque, T. L., Ishimori, T., Konishi, J., Togashi, K., & Brechbiel, M. W. (2001b). Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer. Bioconjug Chem, 12(1), 100–107.Google Scholar
  69. Kolhatkar, K., Kitchens, K. M., Swaan, P. & Ghandehari, H. (2007), Surface acetylation of poly(amidoamine) (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability, Bioconjugate Chemistry, 18, 2054–2060.Google Scholar
  70. Kolhe, P., Khandare, J., Pillai, O., Kannan, S., Lieh-Lai, M., & Kannan, R. M. (2006). Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload. Biomaterials, 27(4), 660–669.PubMedGoogle Scholar
  71. Kolhe, P., Khandare, J., Pillai, O., Kannan, S., Lieh-Lai, M., & Kannan, R. (2004). Hyperbranched polymer-drug conjugates with high drug payload for enhanced cellular delivery. Pharm Res, 21(12), 2185–2195.PubMedGoogle Scholar
  72. Kolhe, P., Misra, E., Kannan, R. M., Kannan, S., & Lieh-Lai, M. (2003). Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int J Pharm, 259(1–2), 143–160.PubMedGoogle Scholar
  73. Konda, S. D., Aref, M., Brechbiel, M., & Wiener, E. C. (2000). Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor: Work in progress. Invest Radiol, 35(1), 50–57.PubMedGoogle Scholar
  74. Langereis, S., de Lussanet, Q. G., van Genderen, M. H., Meijer, E. W., Beets-Tan, R. G., Griffioen, A. W., van Engelshoven, J. M., & Backes, W. H. (2006). Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging. NMR Biomed, 19(1), 133–141.PubMedGoogle Scholar
  75. Launay, N., Caminade, A. M., & Majoral, J. P. (1995). Synthesis and reactivity of unusual phosphorus dendrimers. A useful divergent growth approach up to the seventh generation. J Am Chem Soc, 117(11), 3282–3283.Google Scholar
  76. Lee, C. C., MacKay, J. A., Frechet, J. M., & Szoka, F. C. (2005). Designing dendrimers for biological applications. Nat Biotechnol, 23(12), 1517–1526.PubMedGoogle Scholar
  77. Liu, M., & Frechet, J. M. (1999). Designing dendrimers for drug delivery. Pharm Sci Technol Today, 2(10), 393–401.PubMedGoogle Scholar
  78. Liu, M., Kono, K., & Frechet, J. M. (2000). Water-soluble dendritic unimolecular micelles: Their potential as drug delivery agents. J Control Release, 65(1–2), 121–131.PubMedGoogle Scholar
  79. Loup, C., Zanta, M. A., Caminade, A. M., Majoral, J. P., & Meunier, B. (1999). Preparation of water soluble cationic phosphorous containing dendrimers as DNA transfecting agents. Chem Eur J, 5(12), 3644–3650.Google Scholar
  80. Luo, Y., & Prestwich, G. D. (2002). Cancer-targeted polymeric drugs. Curr Cancer Drug Targets, 2(3), 209–226.PubMedGoogle Scholar
  81. Majoros, I. J., Myc, A., Thomas, T., Mehta, C. B., & Baker, J. R., Jr. (2006). PAMAM dendrimer-based multifunctional conjugate for cancer therapy: Synthesis, characterization, and functionality. Biomacromolecules, 7(2), 572–579.PubMedGoogle Scholar
  82. Malik, N., Evagorou, E. G., & Duncan, R. (2000). Dendrimers: Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release, 65(1–2), 133–148.PubMedGoogle Scholar
  83. Malik, N., Evagorou, E. G., & Duncan, R. (1999). Dendrimer-platinate: A novel approach to cancer chemotherapy. Anticancer Drugs, 10(8), 767–776.PubMedGoogle Scholar
  84. Maraval, V., Pyzowski, J., Caminade, A. M., & Majoral, J. P. (2003). “Lego” chemistry for the straightforward synthesis of dendrimers. J Org Chem, 68, 6043–6046.PubMedGoogle Scholar
  85. Mecke, A., Majoros, I. J., Patri, A. K., Baker, J. R., Jr., Holl, M. M., & Orr, B. G. (2005). Lipid bilayer disruption by polycationic polymers: The roles of size and chemical functional group. Langmuir, 21(23), 10348–10354.PubMedGoogle Scholar
  86. Mecke, A., Uppuluri, S., Sassanella, T. M., Lee, D. K., Ramamoorthy, A., Baker, J. R., Jr., Orr, B. G., & Banaszak Holl, M. M. (2004). Direct observation of lipid bilayer disruption by poly (amidoamine) dendrimers. Chem Phys Lipids, 132(1), 3–14.PubMedGoogle Scholar
  87. Milhem, O. M., Myles, C., McKeown, N. B., Attwood, D., & D'Emanuele, A. (2000). Polyamidoamine starburst dendrimers as solubility enhancers. Int J Pharm, 197(1–2), 239–241.PubMedGoogle Scholar
  88. Namazi, H., & Adeli, M. (2005). Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents. Biomaterials, 26(10), 1175–1183.PubMedGoogle Scholar
  89. Padilla De Jesus, O. L., Ihre, H. R., Gagne, L., Frechet, J. M., & Szoka, F. C., Jr. (2002). Polyester dendritic systems for drug delivery applications: In vitro and in vivo evaluation. Bioconjug Chem, 13(3), 453–461.Google Scholar
  90. Patri, A. K., Kukowska-Latallo, J. F., & Baker, J. R., Jr. (2005). 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.PubMedGoogle Scholar
  91. Potschke, D., Ballauff, M., Lindner, P., Fischer, M., & Vogtle, F. (1999). Analysis of the structure of dendrimers in solution by small-angle neutron scattering including contrast variation. Macromolecules, 32(12), 4079–4087.Google Scholar
  92. Prosa, T. J., Bauer, B. J., & Amis, E. J. (2001). From stars to spheres: A SAXS analysis of dilute dendrimer solutions. Macromolecules, 34(14), 4897–4906.Google Scholar
  93. Quintana, A., Raczka, E., Piehler, L., Lee, I., Myc, A., Majoros, I., Patri, A. K., Thomas, T., Mule, J., & Baker, J. R., Jr. (2002). Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res, 19(9), 1310–1316.PubMedGoogle Scholar
  94. Rajca, A. (1991). Synthesis of 1,3-connected polyarylmethanes. J Org Chem, 56(7), 2557–2563.Google Scholar
  95. Rathgeber, S., Pakula, T., & Urban, V. (2004). Structure of star-burst dendrimers: A comparison between small angle x-ray scattering and computer simulation results. J Chem Phys, 121(8), 3840–3853.PubMedGoogle Scholar
  96. Roberts, J. C., Bhalgat, M. K., & Zera, R. T. (1996). Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. J Biomed Mater Res, 30(1), 53–65.PubMedGoogle Scholar
  97. Rosenfeldt, S., Karpuk, E., Lehmann, M., Meier, H., Lindner, P., Harnau, L., & Ballauff, M. (2006). The solution structure of stilbenoid dendrimers: A small-angle scattering study. Chemphyschem, 7(10), 2097–2104.PubMedGoogle Scholar
  98. Sadler, K., & Tam, J.P. (2002). Peptide dendrimers: Applications and synthesis. J Biotechnol, 90(3–4), 195–229.PubMedGoogle Scholar
  99. Sakamoto, Y., Suzuki, T., Miura, A., Fujikawa, H., Tokito, S., & Taga, Y. (2000). Synthesis, characterization, and electron-transport property of perfluorinated phenylene dendrimers. J Am Chem Soc, 122(8), 1832–1833.Google Scholar
  100. Sakthivel, T., Toth, I., & Florence, A. T. (1999). Distribution of a lipidic 2.5 nm diameter dendrimer carrier after oral administration. Int J Pharm, 183(1), 51–55.PubMedGoogle Scholar
  101. Sanchez-Sancho, F., Perez-Inestrosa, E., Suau, R., Mayorga, C., Torres, M. J., & Blanca, M. (2002). Dendrimers as carrier protein mimetics for Ige antibody recognition. Synthesis and characterization of densely penicilloylated dendrimers. Bioconjug Chem, 13(3), 647–653.PubMedGoogle Scholar
  102. Sedlakova, P., Svobodova, J., Miksik, I., & Tomas, H. (2006). Separation of poly(amidoamine) (PAMAM) dendrimer generations by dynamic coating capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci, 841(1–2), 135–139.PubMedGoogle Scholar
  103. Shaunak, S., Thomas, S., Gianasi, E., Godwin, A., Jones, E., Teo, I., Mireskandari, K., Luthert, P., Duncan, R., Patterson, S., Khaw, P., & Brocchini, S. (2004). Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation. Nat Biotechnol, 22(8), 977–984.PubMedGoogle Scholar
  104. Shi, X., Patri, A. K., Lesniak, W., Islam, M. T., Zhang, C., Baker, J. R., Jr., & Balogh, L. P. (2005). Analysis of poly(amidoamine)-succinamic acid dendrimers by slab-gel electrophoresis and capillary zone electrophoresis. Electrophoresis, 26(15), 2960–2967.PubMedGoogle Scholar
  105. Singh, B., & Florence, A. T. (2005). Hydrophobic dendrimer-derived nanoparticles. Int J Pharm, 298(2), 348–353.PubMedGoogle Scholar
  106. Svenson, S., & Tomalia, D. A. (2005). Dendrimers in biomedical applications – reflections on the field. Adv Drug Deliv Rev, 57(15), 2106–2129.PubMedGoogle Scholar
  107. Tack, F., Bakker, A., Maes, S., Dekeyser, N., Bruining, M., Elissen-Roman, C., Janicot, M., Brewster, M., Janssen, H. M., de Waal, B. F., Fransen, P. M., Lou, X., & Meijer, E. W. (2006). Modified poly(propylene imine) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes). J Drug Target, 14(2), 69–86.PubMedGoogle Scholar
  108. Tajarobi, F., El-Sayed, M., Rege, B. D., Polli, J. E., & Ghandehari, H. (2001). Transport of poly amidoamine dendrimers across Madin-Darby canine kidney cells. Int J Pharm, 215(1–2), 263–267.PubMedGoogle Scholar
  109. Takakura, Y., Mahato, R. I., & Hashida, M. (1998). Extravasation of macromolecules. Adv Drug Deliv Rev, 34(1), 93–108.PubMedGoogle Scholar
  110. Tang, M. X., Redemann, C. T., & Szoka, F. C., Jr. (1996). In vitro gene delivery by degraded polyamidoamine dendrimers. Bioconjug Chem, 7(6), 703–714.PubMedGoogle Scholar
  111. Tang, S., Martinez, L. J., Sharma, A., & Chai, M. (2006). Synthesis and characterization of water-soluble and photostable L-DOPA dendrimers. Org Lett, 8, 4421–4424.PubMedGoogle Scholar
  112. Tansey, W., Ke, S., Cao, X. Y., Pasuelo, M. J., Wallace, S., & Li, C. (2004). Synthesis and characterization of branched poly(L-glutamic acid) as a biodegradable drug carrier. J Control Release, 94(1), 39–51.PubMedGoogle Scholar
  113. Tomalia, D. A. (1993). StarburstTM/cascade dendrimers: Fundamental building bocks for new nanoscopic chemistry set. Aldrichimica Acta, 26(4), 91–101.Google Scholar
  114. Tomalia, D. A. (2004). Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic organic chemistry. Aldrichimica Acta, 37(2), 39–57.Google Scholar
  115. Tomalia, D. A., Naylor, A. M., & Goddard III, W. A. (1990). Starburst dendrimers. Molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew Chem Int Ed Engl, 29(2), 138–175.Google Scholar
  116. Tomlinson, R., Heller, J., Brocchini, S., & Duncan, R. (2003). Polyacetal-doxorubicin conjugates designed for pH-dependent degradation. Bioconjug Chem, 14(6), 1096–1106.PubMedGoogle Scholar
  117. Torchilin, V. P. (2006). Multifunctional nanocarriers. Adv Drug Deliv Rev, 58(14), 1532–1555.PubMedGoogle Scholar
  118. Trewhella, J., Gallagher, S. C., Krueger, J. K., & Zhao, J. (1998). Neutron and x-ray solution scattering provide insights into biomolecular structure and function. Sci Prog, 81(Pt 2), 101–122.PubMedGoogle Scholar
  119. Turnbull, W. B., & Stoddart, J. F. (2002). Design and synthesis of glycodendrimers. J Biotechnol, 90(3–4), 231–255.PubMedGoogle Scholar
  120. Velazquez, A. J., Carnahan, M. A., Kristinsson, J., Stinnett, S., Grinstaff, M. W., & Kim, T. (2004). New dendritic adhesives for sutureless ophthalmic surgical procedures: In vitro studies of corneal laceration repair. Arch Ophthalmol, 122(6), 867–870.PubMedGoogle Scholar
  121. Wang, S. J., Brechbiel, M., & Wiener, E. C. (2003). Characteristics of a new MRI contrast agent prepared from polypropyleneimine dendrimers, generation 2. Invest Radiol, 38(10), 662–668.PubMedGoogle Scholar
  122. Wiener, E. C., Brechbiel, M. W., Brothers, H., Magin, R. L., Gansow, O. A., Tomalia, D. A., & Laterbur, P. C. (1994). Dendrimer-based metal chelates: A new class of magnetic resonance imaging contrast agents. Magn Reson Med, 31(1), 1–8.PubMedGoogle Scholar
  123. Wignall, G. D., & Melnichenko, Y. B. (2005). Recent applications of small-angle neutron scattering in strongly interacting soft condensed matter. Rep Prog Phys, 68(8), 1761–1810.Google Scholar
  124. Wiwattanapatapee, R., Carreno-Gomez, B., Malik, N., & Duncan, R. (2000). Anionic PAMAM dendrimers rapidly cross adult rat intestine in vitro: A potential oral delivery system? Pharm Res, 17(8), 991–998.PubMedGoogle Scholar
  125. Wu, P., Malkoch, M., Hunt, J. N., Vestberg, R., Kaltgrad, E., Finn, M. G., Fokin, V. V., Sharpless, K. B., & Hawker, C. J. (2005). Multivalent, bifunctional dendrimers prepared by click chemistry. Chem Commun (Camb) (46), 5775–5777.Google Scholar
  126. Wu, P., Feldman, A. K., Nugent, A. K., Hawker, C. J., Scheel, A., Voit, B., Pyun, J., Frechet, J. M., Sharpless, K. B., & Fokin, V. V. (2004a). Efficiency and fidelity in a click-chemistry route to triazole dendrimers by the copper(I)-catalyzed ligation of azides and alkynes. Angew Chem Int Ed Engl, 43(30), 3928–3932.Google Scholar
  127. Wu, X. Y., Huang, S. W., Zhang, J. T., & Zhuo, R. X. (2004b). Preparation and characterization of novel physically cross-linked hydrogels composed of poly(vinyl alcohol) and amine-terminated polyamidoamine dendrimer. Macromol Biosci, 4(2), 71–75.Google Scholar
  128. Yoo, H., & Juliano, R. L. (2000). Enhanced delivery of antisense oligonucleotides with fluorophore-conjugated PAMAM dendrimers. Nucleic Acids Res, 28(21), 4225–4231.PubMedGoogle Scholar
  129. Yordanov, A. T., Lodder, A. L., Woller, E. K., Cloninger, M. J., Patronas, N., Milenic, D., & Brechbiel, M. W. (2002). Novel iodinated dendritic nanoparticles for computed tomography (CT) imaging. Nano Lett, 2(6), 595–599.Google Scholar
  130. Zhuo, R. X., Du, B., & Lu, Z. R. (1999). In vitro release of 5-fluorouracil with cyclic core dendritic polymer. J Control Release, 57(3), 249–257.PubMedGoogle Scholar
  131. Ziemer, L. S., Lee, W. M., Vinogradov, S. A., Sehgal, C., & Wilson, D. F. (2005). Oxygen distribution in murine tumors: Characterization using oxygen-dependent quenching of phosphorescence. J Appl Physiol, 98(4), 1503–1510.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Kelly M. Kitchens
    • 1
  • Hamidreza Ghandehari
    • 2
  1. 1.Alba Therapeutics CorporationDiscovery and Preclinical DevelopmentBaltimoreUSA
  2. 2.Department of Pharmaceutics and Pharmaceutical Chemistry and BioengineeringUniversity of UtahSalt Lake CityUSA

Personalised recommendations