Advertisement

Archives of Pharmacal Research

, Volume 41, Issue 6, pp 571–582 | Cite as

Recent progress in dendrimer-based nanomedicine development

  • Yejin Kim
  • Eun Ji Park
  • Dong Hee Na
Review

Abstract

Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural properties of dendrimers have created many applications for drug and gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers are not only capable of delivering drugs or diagnostic agents to desired sites by encapsulating or conjugating them to the periphery, but also have therapeutic efficacy in their own. When compared to traditional polymers for drug delivery, dendrimers have distinct advantages, such as high drug-loading capacity at the surface terminal for conjugation or interior space for encapsulation, size control with well-defined numbers of peripheries, and multivalency for conjugation to drugs, targeting moieties, molecular sensors, and biopolymers. This review focuses on recent applications of dendrimers for the development of dendrimer-based nanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still face some challenges including scale-up production and well-characterization, several dendrimer-based drug candidates are expected to enter clinical development phase in the near future.

Keywords

Dendrimer Drug delivery Nanoarchitecture Nanomedicine Nanotechnology 

Notes

Acknowledgements

This research was supported by the Chung-Ang University Research Scholarship Grants in 2017. This work was supported by the National Research Foundation of Korea (NRF) Grants funded by the Ministry of Education (NRF-2016R1D1A1B03934847).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Abdoli A, Radmehr N, Bolhassani A, Eidi A, Mehrbod P, Motevalli F, Kianmehr Z, Chiani M, Mahdavi M, Yazdani S, Ardestani MS, Kandi MR, Aghasadeghi MR (2017) Conjugated anionic PEG-citrate G2 dendrimer with multi-epitopic HIV-1 vaccine candidate enhance the cellular immune responses in mice. Artif Cells Nanomed Biotechnol 45:1762–1768PubMedGoogle Scholar
  2. Akhtar S, Al-Zaid B, El-Hashim AZ, Chandrasekhar B, Attur S, Benter IF (2016) Impact of PAMAM delivery systems on signal transduction pathways in vivo: modulation of ERK1/2 and p38 MAP kinase signaling in the normal and diabetic kidney. Int J Pharm 514:353–363PubMedGoogle Scholar
  3. Alarcón GS (2000) Methotrexate use in rheumatoid arthritis. A Clinician’s perspective. Immunopharmacology 47:259–271PubMedGoogle Scholar
  4. Avila-Salas F, Sandoval C, Caballero J, Guiñez-Molinos S, Santos LS, Cachau RE, González-Nilo FD (2012) Study of interaction energies between the PAMAM dendrimer and nonsteroidal anti-inflammatory drug using a distributed computational strategy and experimental analysis by ESI-MS/MS. J Phys Chem B 116:2031–2039PubMedPubMedCentralGoogle Scholar
  5. Bahadoran A, Ebrahimi M, Yeap SK, Safi N, Moeini H, Hair-Bejo M, Hussein MZ, Omar AR (2017) Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model. Int J Nanomedcine 12:8573–8585Google Scholar
  6. Barth RF, Adams DM, Soloway AH, Alam F, Darby MV (1994) Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. Bioconjug Chem 5:58–66PubMedGoogle Scholar
  7. Barth RF, Coderre JA, Vicente MG, Blue TE (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002PubMedGoogle Scholar
  8. Barth RF, Wu G, Meisen WH, Nakkula RJ, Yang W, Huo T, Kellough DA, Kaumaya P, Turro C, Agius LM, Kaur B (2016) Design, synthesis, and evaluation of cisplatin-containing EGFR targeting bioconjugates as potential therapeutic agents for brain tumors. Onco Targets Ther 9:2769–2781PubMedPubMedCentralGoogle Scholar
  9. Bernstein DI, Stanberry LR, Sacks S, Ayisi NK, Gong YH, Ireland J, Mumper RJ, Holan G, Matthews B, McCarthy T, Bourne N (2003) Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes. Antimicrob Agents Chemother 47:3784–3788PubMedPubMedCentralGoogle Scholar
  10. Bhatia S, Camacho LC, Haag R (2016) Pathogen inhibition by multivalent ligand architectures. J Am Chem Soc 138:8654–8666PubMedGoogle Scholar
  11. Boas U, Heegaard PM (2004) Dendrimers in drug research. Chem Soc Rev 33:43–63PubMedGoogle Scholar
  12. Bosch X (2011) Dendrimers to treat rheumatoid arthritis. ACS Nano 5:6779–6785PubMedGoogle Scholar
  13. Bourne N, Stanberry LR, Kern ER, Holan G, Matthews B, Bernstein DI (2000) Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother 44:2471–2474PubMedPubMedCentralGoogle Scholar
  14. Calixto GM, Bernegossi J, de Freitas LM, Fontana CR, Chorilli M (2016) Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: a review. Molecules 21:342PubMedGoogle Scholar
  15. Capala J, Barth RF, Bendayan M, Lauzon M, Adams DM, Soloway AH, Fenstermaker RA, Carlsson J (1996) Boronated epidermal growth factor as a potential targeting agent for boron neutron capture therapy of brain tumors. Bioconjug Chem 7:7–15PubMedGoogle Scholar
  16. Caster JM, Patel AN, Zhang T, Wang A (2017) Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. WIREs Nanomed Nanobiotechnol 9:e1416Google Scholar
  17. Chang Y, Meng X, Zhao Y, Li K, Zhao B, Zhu M, Li Y, Chen X, Wang J (2011) Novel water-soluble and pH-responsive anticancer drug nanocarriers: doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs). J Colloid Interface Sci 363:403–409PubMedGoogle Scholar
  18. Chauhan AS, Diwan PV, Jain NK, Tomalia DA (2009) Unexpected in vivo anti-inflammatory activity observed for simple, surface functionalized poly(amidoamine) dendrimers. Biomacromol 10:1195–1202Google Scholar
  19. Chen CZ, Cooper SL (2002) Interactions between dendrimer biocides and bacterial membranes. Biomaterials 23:3359–3368PubMedGoogle Scholar
  20. Choi SK, Myc A, Silpe JE, Sumit M, Wong PT, McCarthy K, Desai AM, Thomas TP, Kotlyar A, Holl MM, Orr BG, Baker JR Jr (2013) Dendrimer-based multivalent vancomycin nanoplatform for targeting the drug-resistant bacterial surface. ACS Nano 7:214–228PubMedGoogle Scholar
  21. Choi JY, Thapa RK, Yong CS, Kim JO (2016) Nanoparticle-based combination drug delivery systems for synergistic cancer treatment. J Pharm Investig 46:325–339Google Scholar
  22. Chouai A, Venditto VJ, Simanek EE, Vanderplas BC, Ragan JA (2009) Large scale, green synthesis of a genenration-1 melamine (trazine) dendrimer. Organic Synth 86:151–160PubMedPubMedCentralGoogle Scholar
  23. Davignon JL, Hayder M, Baron M, Boyer JF, Constantin A, Apparailly F, Poupot R, Cantagrel A (2013) Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology 52:590–598PubMedGoogle Scholar
  24. Duncan R, Izzo L (2005) Dendrimer biocompatibility and toxicity. Adv Drug Deliv Rev 57:2215–2237PubMedGoogle Scholar
  25. Durocher I, Girard D (2016) In vivo proinflammatory activity of generations 0–3 (G0-G3) polyamidoamine (PAMAM) nanoparticles. Inflamm Res 65:745–755PubMedGoogle Scholar
  26. Esfand R, Tomalia DA (2001) Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6:427–436PubMedGoogle Scholar
  27. Gajbhiye V, Palanirajan VK, Tekade RK, Jain NK (2009) Dendrimers as therapeutic agents: a systematic review. J Pharm Pharmacol 61:989–1003PubMedGoogle Scholar
  28. Gong Y, Matthews B, Cheung D, Tam T, Gadawski I, Leung D, Holan G, Raff J, Sacks S (2002) Evidence of dual sites of action of dendrimers: SPL-2999 inhibits both virus entry and late stages of herpes simplex virus replication. Antiviral Res 55:319–329PubMedGoogle Scholar
  29. Gupta U, Agashe HB, Asthana A, Jain NK (2006) Dendrimers: novel polymeric nanoarchitectures for solubility enhancement. Biomacromol 7:649–658Google Scholar
  30. Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8:533–544PubMedGoogle Scholar
  31. Hayden F (2009) Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis 48:S3–S13PubMedGoogle Scholar
  32. Hayder M, Poupot M, Baron M, Nigon D, Turrin CO, Caminade AM, Majoral JP, Eisenberg RA, Fournié JJ, Cantagrel A, Poupot R, Davignon JL (2011) A phosphorus-based dendrimer targets inflammation and osteoclastogenesis in experimental arthritis. Sci Transl Med 3:81ra35Google Scholar
  33. He H, Li Y, Jia XR, Du J, Ying X, Lu WL, Lou JN, Wei Y (2011) PEGylated poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials 32:478–487PubMedGoogle Scholar
  34. Hoang NH, Lim C, Sim T, Oh KT (2017) Triblock copolymers for nano-sized drug delivery systems. J Pharm Investig 47:27–35Google Scholar
  35. Hong SH, Choi Y (2018) Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents. J Pharm Investig 48:3–17Google Scholar
  36. Hu J, Su Y, Zhang H, Xu T, Cheng Y (2011) Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery. Biomaterials 32:9950–9959PubMedGoogle Scholar
  37. Huang B, Desai A, Zong H, Tang S, Leroueil P, Baker JR Jr (2011) Copper-free click conjugation of methotrexate to a PAMAM dendrimer platform. Tetrahedron Lett 52:1411–1414PubMedPubMedCentralGoogle Scholar
  38. Jain K, Kesharwani P, Gupta U, Jain NK (2010) Dendrimer toxicity: let’s meet the challenge. Int J Pharm 394:122–142PubMedGoogle Scholar
  39. Jain NK, Tare MS, Mishra V, Tripathi PK (2015) The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel. Nanomedicine 11:207–218PubMedGoogle Scholar
  40. Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB, D’Emanuele A (2003) The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm 252:263–266PubMedGoogle Scholar
  41. Jin Y, Ren X, Wang W, Ke L, Ning E, Du L, Bradshaw J (2011) A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting. Int J Pharm 420:378–384PubMedGoogle Scholar
  42. Kambhampati SP, Mishra MK, Mastorakos P, Oh Y, Lutty GA, Kannan RM (2015) Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells. Eur J Pharm Biopharm 95:239–249PubMedPubMedCentralGoogle Scholar
  43. Kaminskas LM, Kelly BD, McLeod VM, Boyd BJ, Krippner GY, Williams ED, Porter CJ (2009) Pharmacokinetics and tumor disposition of PEGylated, methotrexate conjugated poly-l-lysine dendrimers. Mol Pharm 6:1190–1204PubMedGoogle Scholar
  44. Kaminskas LM, McLeod VM, Porter CJ, Boyd BJ (2012) Association of chemotherapeutic drugs with dendrimer nanocarriers: an assessment of the merits of covalent conjugation compared to noncovalent encapsulation. Mol Pharm 9:355–373PubMedGoogle Scholar
  45. Kaminskas LM, McLeod VM, Ascher DB, Ryan GM, Jones S, Haynes JM, Trevaskis NL, Chan LJ, Sloan EK, Finnin BA, Williamson M, Velkov T, Williams ED, Kelly BD, Owen DJ, Porter CJ (2015) Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats. Mol Pharm 12:432–443PubMedGoogle Scholar
  46. Kannan RM, Nance E, Kannan S, Tomalia DA (2014) Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med 276:579–617PubMedGoogle Scholar
  47. Kesavan A, Ilaiyaraja P, Sofi Beaula W, Veena Kumari V, Sugin Lal J, Arunkumar C, Anjana G, Srinivas S, Ramesh A, Rayala SK, Ponraju D, Venkatraman G (2015) Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin. Eur J Pharm Biopharm 96:255–263PubMedGoogle Scholar
  48. Kesharwani P, Iyer AK (2015) Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery. Drug Discov Today 20:536–547PubMedGoogle Scholar
  49. Khatri S, Das NG, Das SK (2014) Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells. J Pharm Bioallied Sci 6:297–302PubMedPubMedCentralGoogle Scholar
  50. Kim Y, Klutz AM, Jacobson KA (2008) Systematic investigation of polyamidoamine dendrimers surface-modified with poly(ethylene glycol) for drug delivery applications: synthesis, characterization, and evaluation of cytotoxicity. Bioconjug Chem 19:1660–1672PubMedPubMedCentralGoogle Scholar
  51. Kim Y, Park EJ, Na DH (2016) Antibody-drug conjugates for targeted anticancer drug delivery. J Pharm Investig 46:341–349Google Scholar
  52. Kim CH, Lee SG, Kang MJ, Lee S, Choi YW (2017) Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting. J Pharm Investig 47:203–227Google Scholar
  53. Kirkpatrick GJ, Plumb JA, Sutcliffe OB, Flint DJ, Wheate NJ (2011) Evaluation of anionic half generation 3.5-6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin. J Inorg Biochem 105:1115–1122PubMedGoogle Scholar
  54. Klajnert B, Bryszewska M (2001) Dendrimers: properties and applications. Acta Biochim Pol 48:199–208PubMedGoogle Scholar
  55. Klajnert B, Rozanek M, Bryszewska M (2012) Dendrimers in photodynamic therapy. Curr Med Chem 19:4903–4912PubMedGoogle Scholar
  56. Koç FE, Senel M (2013) Solubility enhancement of non-steroidal anti-inflammatory drugs (NSAIDs) using polypolypropylene oxide core PAMAM dendrimers. Int J Pharm 451:18–22PubMedGoogle Scholar
  57. Kojima C, Regino C, Umeda Y, Kobayashi H, Kono K (2010) Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers. Int J Pharm 383:293–296PubMedGoogle Scholar
  58. Kulhari H, Pooja D, Singh MK, Chauhan AS (2015) Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation. Drug Dev Ind Pharm 41:232–238PubMedGoogle Scholar
  59. Kurtoglu YE, Navath RS, Wang B, Kannan S, Romero R, Kannan RM (2009) Poly(amidoamine) dendrimer–drug conjugates with disulfide linkages for intracellular drug delivery. Biomaterials 30:2112–2121PubMedPubMedCentralGoogle Scholar
  60. Kwon SJ, Na DH, Kwak JH, Douaisi M, Zhang F, Park EJ, Park JH, Youn H, Song CS, Kane RS, Dordick JS, Lee KB, Linhardt RJ (2017) Nanostructured glycan architecture is important in the inhibition of influenza A virus infection. Nat Nanotechnol 12:48–54PubMedGoogle Scholar
  61. Ladd E, Sheikhi A, Li N, van de Ven TGM, Kakkar A (2017) Design and synthesis of dendrimers with facile surface group functionalization, and an evaluation of their bactericidal efficacy. Molecules 22:868Google Scholar
  62. Landarani-Isfahani A, Moghadam M, Mohammadi S, Royvaran M, Moshtael-Arani N, Rezaei S, Tangestaninejad S, Mirkhani V, Mohammadpoor-Baltork I (2017) Elegant pH-responsive nanovehicle for drug delivery based on triazine dendrimer modified magnetic nanoparticles. Langmuir 33:8503–8515PubMedGoogle Scholar
  63. Landers JJ, Cao Z, Lee I, Piehler LT, Myc PP, Myc A, Hamouda T, Galecki AT, Baker JR Jr (2002) Prevention of influenza pneumonitis by sialic acid-conjugated dendritic polymers. J Infect Dis 186:1222–1230PubMedGoogle Scholar
  64. Lee CC, MacKay JA, Fréchet JM, Szoka FC (2005) Designing dendrimers for biological applications. Nat Biotechnol 23:1517–1526PubMedGoogle Scholar
  65. Lei J, Rosenzweig JM, Mishra MK, Alshehri W, Brancusi F, McLane M, Almalki A, Bahabry R, Arif H, Rozzah R, Alyousif G, Shabi Y, Alhehaily N, Zhong W, Facciabene A, Kannan S, Kannan RM, Burd I (2017) Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury. Sci Rep 7:6106PubMedPubMedCentralGoogle Scholar
  66. Leiro V, Garcia JP, Tomás H, Pêgo AP (2015) The present and the future of degradable dendrimers and derivatives in theranostics. Bioconjug Chem 26:1182–1197PubMedGoogle Scholar
  67. Li Y, He H, Jia X, Lu WL, Lou J, Wei Y (2012) A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials 33:3899–3908PubMedGoogle Scholar
  68. Li N, Cai H, Jiang L, Hu J, Bains A, Hu J, Gong Q, Luo K, Gu Z (2017a) Enzyme-sensitive and amphiphilic PEGylated dendrimer-paclitaxel prodrug-based nanoparticles for enhanced stability and anticancer efficacy. ACS Appl Mater Interfaces 9:6865–6877PubMedGoogle Scholar
  69. Li Y, He H, Lu W, Jia X (2017b) A poly(amidoamine) dendrimer-based drug carrier for delivering DOX to gliomas cells. RSC Adv 7:15475–15481Google Scholar
  70. Lim LY, Koh PY, Somani S, Al Robaian M, Karim R, Yean YL, Mitchell J, Tate RJ, Edrada-Ebel R, Blatchford DR, Mullin M, Dufès C (2015) Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes. Nanomedicine 11:1445–1454PubMedPubMedCentralGoogle Scholar
  71. Ly TU, Tran NQ, Hoang TK, Phan KN, Truong HN, Nguyen CK (2013) Pegylated dendrimer and its effect in fluorouracil loading and release for enhancing antitumor activity. J Biomed Nanotechnol 9:213–220PubMedGoogle Scholar
  72. Ma P, Zhang X, Ni L, Li J, Zhang F, Wang Z, Lian S, Sun K (2015) Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab. Int J Nanomedcine 10:2173–2190Google Scholar
  73. Maeda H (2017) Polymer therapeutics and the EPR effect. J Drug Target 25:781–785PubMedGoogle Scholar
  74. Mastorakos P, Kambhampati SP, Mishra MK, Wu T, Song E, Hanes J, Kannan RM (2015) Hydroxyl PAMAM dendrimer-based gene vectors for transgene delivery to human retinal pigment epithelial cells. Nanoscale 7:3845–3856PubMedPubMedCentralGoogle Scholar
  75. Matai I, Sachdev A, Gopinath P (2015) Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells. Biomater Sci 3:457–468PubMedGoogle Scholar
  76. McCarthy TD, Karellas P, Henderson SA, Giannis M, O’Keefe DF, Heery G, Paull JR, Matthews BR, Holan G (2005) Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention. Mol Pharm 2:312–318PubMedGoogle Scholar
  77. Medina SH, El-Sayed ME (2009) Dendrimers as carriers for delivery of chemotherapeutic agents. Chem Rev 109:3141–3157PubMedGoogle Scholar
  78. Mehendale R, Joshi M, Patravale VB (2013) Nanomedicines for treatment of viral diseases. Crit Rev Ther Drug Carrier Syst 30:1–49PubMedGoogle Scholar
  79. Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15:171–185PubMedGoogle Scholar
  80. Michiue H, Sakurai Y, Kondo N, Kitamatsu M, Bin F, Nakajima K, Hirota Y, Kawabata S, Nishiki T, Ohmori I, Tomizawa K, Miyatake S, Ono K, Matsui H (2014) The acceleration of boron neutron capture therapy using multi-linked mercaptoundecahydrododecaborate (BSH) fused cell-penetrating peptide. Biomaterials 35:3396–3405PubMedGoogle Scholar
  81. Mintzer MA, Dane EL, O’Toole GA, Grinstaff MW (2012) Exploiting dendrimer multivalency to combat emerging and re-emerging infectious diseases. Mol Pharm 9:342–354PubMedGoogle Scholar
  82. Nakamura Y, Mochida A, Choyke PL, Kobayashi H (2016) Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 27:2225–2238PubMedGoogle Scholar
  83. Nakashima-Matsushita N, Homma T, Yu S, Matsuda T, Sunahara N, Nakamura T, Tsukano M, Ratnam M, Matsuyama T (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616PubMedGoogle Scholar
  84. Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, Johnston MV, Rangaramanujam K, Blue ME, Kannan S (2017) Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome. J Neuroinflamm 14:252Google Scholar
  85. Narsireddy A, Vijayashree K, Adimoolam MG, Manorama SV, Rao NM (2015) Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy. Int J Nanomedcine 10:6865–6878Google Scholar
  86. Navath RS, Kurtoglu YE, Wang B, Kannan S, Romero R, Kannan RM (2008) Dendrimer-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjug Chem 19:2446–2455PubMedPubMedCentralGoogle Scholar
  87. Neibert K, Gosein V, Sharma A, Khan M, Whitehead MA, Maysinger D, Kakkar A (2013) “Click” dendrimers as anti-inflammatory agents: with insights into their binding from molecular modeling studies. Mol Pharm 10:2502–2508PubMedGoogle Scholar
  88. Park EJ, Na DH (2014) Palmitoylation of octreotide for incorporation into poly(amidoamine) dendrimers. J Pharm Investig 44:141–145Google Scholar
  89. Park EJ, Na DH (2015) Difference in microchip electrophoretic mobility between partially and fully PEGylated poly(amidoamine) dendrimers. Anal Biochem 488:9–11PubMedGoogle Scholar
  90. Park EJ, Cho H, Kim SW, Na DH (2014) Chromatographic methods for characterization of poly(ethylene glycol)-modified polyamidoamine dendrimers. Anal Biochem 449:42–44PubMedGoogle Scholar
  91. Park EJ, Kim JE, Kim DK, Park JH, Lee KB, Na DH (2016) Glucosamine-conjugated anionic poly(amidoamine) dendrimers inhibit interleukin-8 production by Helicobacter pylori in gastric epithelial cells. Bull Korean Chem Soc 37:596–599Google Scholar
  92. Park O, Yu G, Jung H, Mok H (2017) Recent studies on micro-/nano-sized biomaterials for cancer immunotherapy. J Pharm Investig 47:11–18Google Scholar
  93. Price CF, Tyssen D, Sonza S, Davie A, Evans S, Lewis GR, Xia S, Spelman T, Hodsman P, Moench TR, Humberstone A, Paull JR, Tachedjian G (2011) SPL7013 Gel (VivaGel®) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. PLoS One 6:e24095PubMedPubMedCentralGoogle Scholar
  94. Qi R, Majoros I, Misra AC, Koch AE, Campbell P, Marotte H, Bergin IL, Cao Z, Goonewardena S, Morry J, Zhang S, Beer M, Makidon P, Kotlyar A, Thomas TP, Baker JR Jr (2015) Folate receptor-targeted dendrimer-methotrexate conjugate for inflammatory arthritis. J Biomed Nanotechnol 11:1431–1441PubMedGoogle Scholar
  95. Qi X, Qin J, Fan Y, Qin X, Jiang Y, Wu Z (2016) Carboxymethyl chitosan-modified polyamidoamine dendrimer enables progressive drug targeting of tumors via pH-sensitive charge inversion. J Biomed Nanotechnol 12:667–678PubMedGoogle Scholar
  96. Quintana A, Raczka E, Piehler L, Lee I, Myc A, Majoros I, Patri AK, Thomas T, Mulé J, Baker JR Jr (2002) Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm Res 19:1310–1316PubMedGoogle Scholar
  97. Reuter JD, Myc A, Hayes MM, Gan Z, Roy R, Qin D, Yin R, Piehler LT, Esfand R, Tomalia DA, Baker JR Jr (1999) Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers. Bioconjug Chem 10:271–278PubMedGoogle Scholar
  98. Ryan GM, McLeod VM, Mehta D, Kelly BD, Stanislawski PC, Owen DJ, Kaminskas LM, Porter CJH (2017) Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site. Nanomedicine 13:2485–2494PubMedGoogle Scholar
  99. Safavi MS, Shojaosadati SA, Yang HG, Kim Y, Park EJ, Lee KC, Na DH (2017) Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature. Int J Pharm 529:303–309PubMedGoogle Scholar
  100. Schumann C, Taratula O, Khalimonchuk O, Palmer AL, Cronk LM, Jones CV, Escalante CA, Taratula O (2015) ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression. Nanomedicine 11:1961–1970PubMedGoogle Scholar
  101. Sepúlveda-Crespo D, Gómez R, De La Mata FJ, Jiménez JL, Muñoz-Fernández MÁ (2015) Polyanionic carbosilane dendrimer-conjugated antiviral drugs as efficient microbicides: recent trends and developments in HIV treatment/therapy. Nanomedicine 11:1481–1498PubMedGoogle Scholar
  102. Sepúlveda-Crespo D, Ceña-Díez R, Jiménez JL, Ángeles Muñoz-Fernández M (2017) Mechanistic studies of viral entry: an overview of dendrimer-based microbicides as entry inhibitors against both HIV and HSV-2 overlapped infections. Med Res Rev 37:149–179PubMedGoogle Scholar
  103. Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U (2017) Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery. Drug Discov Today 22:314–326PubMedGoogle Scholar
  104. Shaunak S (2015) Perspective: dendrimer drugs for infection and inflammation. Biochem Biophys Res Commun 468:435–441PubMedGoogle Scholar
  105. 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 22:977–984PubMedGoogle Scholar
  106. Shcharbin D, Shcharbina N, Dzmitruk V, Pedziwiatr-Werbicka E, Ionov M, Mignani S, de la Mata FJ, Gómez R, Muñoz-Fernández MA, Majoral JP, Bryszewska M (2017) Dendrimer-protein interactions versus dendrimer-based nanomedicine. Colloids Surf B Biointerfaces 152:414–422PubMedGoogle Scholar
  107. Sim T, Lim C, Hoang NH, Joo H, Lee JW, Kim D, Lee ES, Youn YS, Kim JO, Oh KT (2016) Nanomedicines for oral administration based on diverse nanoplatform. J Pharm Investig 46:351–362Google Scholar
  108. Singh P (2007) Dendrimers and their applications in immunoassays and clinical diagnostics. Biotechnol Appl Biochem 48:1–9PubMedGoogle Scholar
  109. Singh L, Kruger HG, Maguire GEM, Govender T, Parboosing R (2017) The role of nanotechnology in the treatment of viral infections. Ther Adv Infect Dis 4:105–131PubMedPubMedCentralGoogle Scholar
  110. Sk UH, Kojima C (2015) Dendrimers for theranostic applications. Biomol Concepts 6:205–217PubMedGoogle Scholar
  111. Soler M, Mesa-Antunez P, Estevez MC, Ruiz-Sanchez AJ, Otte MA, Sepulveda B, Collado D, Mayorga C, Torres MJ, Perez-Inestrosa E, Lechuga LM (2015) Highly sensitive dendrimer-based nanoplasmonic biosensor for drug allergy diagnosis. Biosens Bioelectron 66:115–123PubMedGoogle Scholar
  112. Son S, Lim SM, Chae SY, Kim K, Park EJ, Lee KC, Na DH (2015) Mono-lithocholated exendin-4-loaded glycol chitosan nanoparticles with prolonged antidiabetic effects. Int J Pharm 495:81–86PubMedGoogle Scholar
  113. Soto-Castro D, Cruz-Morales JA, Apan MTR, Guadarrama P (2012) Solubilization and anticancer-activity enhancement of Methotrexate by novel dendrimeric nanodevices synthesized in one-step reaction. Bioorg Chem 41:13–21PubMedGoogle Scholar
  114. Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications—reflections on the field. Adv Drug Deliv Rev 57:2106–2129PubMedGoogle Scholar
  115. Teow HM, Zhou Z, Najlah M, Yusof SR, Abbott NJ, D’Emanuele A (2013) Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier. Int J Pharm 441:701–711PubMedGoogle Scholar
  116. Thomas TP, Majoros IJ, Kotlyar A, Kukowska-Latallo JF, Bielinska A, Myc A, Baker JR Jr (2005) Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J Med Chem 48:3729–3735PubMedGoogle Scholar
  117. Thomas TP, Goonewardena SN, Majoros IJ, Kotlyar A, Cao Z, Leroueil PR, Baker JR Jr (2011) Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheum 63:2671–2680PubMedPubMedCentralGoogle Scholar
  118. Tomalia DA, Fréchet JM (2002) Discovery of dendrimers and dendritic polymers: a brief historical perspective. J Polym Sci Part A: Polym Chem 40:2719–2728Google Scholar
  119. Wang Q, Li J, An S, Chen Y, Jiang C, Wang X (2015) Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer. Int J Nanomedcine 10:4479–4490Google Scholar
  120. Wang J, He H, Cooper RC, Yang H (2017) In situ-forming polyamidoamine dendrimer hydrogels with tunable properties prepared via aza-michael addition reaction. ACS Appl Mater Interfaces 9:10494–10503PubMedPubMedCentralGoogle Scholar
  121. Wiley DC, Skehel JJ (1987) The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 56:365–394PubMedGoogle Scholar
  122. Witvrouw M, Fikkert V, Pluymers W, Matthews B, Mardel K, Schols D, Raff J, Debyser Z, De Clercq E, Holan G, Pannecouque C (2000) Polyanionic (i.e., polysulfonate) dendrimers can inhibit the replication of human immunodeficiency virus by interfering with both virus adsorption and later steps (reverse transcriptase/integrase) in the virus replicative cycle. Mol Pharmacol 58:1100–1108PubMedGoogle Scholar
  123. Wu G, Barth RF, Yang W, Chatterjee M, Tjarks W, Ciesielski MJ, Fenstermaker RA (2004) Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy. Bioconjug Chem 15:185–194PubMedGoogle Scholar
  124. Wu LP, Ficker M, Christensen JB, Trohopoulos PN, Moghimi SM (2015) Dendrimers in medicine: therapeutic concepts and pharmaceutical challenges. Bioconjug Chem 26:1198–1211PubMedGoogle Scholar
  125. Xue X, Shi X, Dong H, You S, Cao H, Wang K, Wen Y, Shi D, He B, Li Y (2018) Delivery of MicroRNA-1 Inhibitor by dendrimer-based nanovector: an early targeting therapy for myocardial infarction in mice. Nanomedicine 14:619–631PubMedGoogle Scholar
  126. Yang H (2016) Targeted nanosystems: advances in targeted dendrimers for cancer therapy. Nanomedicine 12:309–316PubMedGoogle Scholar
  127. Yang R, Mao Y, Ye T, Xia S, Wang S, Wang S (2016) Study on enhanced lymphatic exposure of polyamidoamin-alkali blue dendrimer for paclitaxel delivery and influence of the osmotic pressure on the lymphatic targeting. Drug Deliv 23:2617–2629PubMedGoogle Scholar
  128. Yellepeddi VK, Kumar A, Maher DM, Chauhan SC, Vangara KK, Palakurthi S (2011) Biotinylated PAMAM dendrimers for intracellular delivery of cisplatin to ovarian cancer: role of SMVT. Anticancer Res 31:897–906PubMedGoogle Scholar
  129. Zhang L, Zhu S, Qian L, Pei Y, Qiu Y, Jiang Y (2011a) RGD-modified PEG-PAMAM-DOX conjugates: in vitro and in vivo studies for glioma. Eur J Pharm Biopharm 79:232–240PubMedGoogle Scholar
  130. Zhang Y, Thomas TP, Lee KH, Li M, Zong H, Desai AM, Kotlyar A, Huang B, Holl MM, Baker JR Jr (2011b) Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conjugate as a potential anticancer agent. Bioorg Med Chem 19:2557–2564PubMedPubMedCentralGoogle Scholar
  131. Zhang F, Nance E, Zhang Z, Jasty V, Kambhampati SP, Mishra MK, Burd I, Romero R, Kannan S, Kannan RM (2016a) Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers. J Control Release 237:61–70PubMedPubMedCentralGoogle Scholar
  132. Zhang F, Nance E, Alnasser Y, Kannan R, Kannan S (2016b) Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation. J Neuroinflammation 13:65PubMedPubMedCentralGoogle Scholar
  133. Zheng W, Cao C, Liu Y, Yu Q, Zheng C, Sun D, Ren X, Liu J (2015) Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance. Acta Biomater 11:368–380PubMedGoogle Scholar
  134. Zhong D, Tu Z, Zhang X, Li Y, Xu X, Gu Z (2017) Bioreducible peptide-dendrimeric nanogels with abundant expanded voids for efficient drug entrapment and delivery. Biomacromolecules 18:3498–3505PubMedGoogle Scholar
  135. Zhu S, Hong M, Tang G, Qian L, Lin J, Jiang Y, Pei Y (2010) Partly PEGylated polyamidoamine dendrimer for tumor-selective targeting of doxorubicin: the effects of PEGylation degree and drug conjugation style. Biomaterials 31:1360–1371PubMedGoogle Scholar
  136. Zong H, Thomas TP, Lee KH, Desai AM, Li MH, Kotlyar A, Zhang Y, Leroueil PR, Gam JJ, Banaszak Holl MM, Baker JR Jr (2012) Bifunctional PAMAM dendrimer conjugates of folic acid and methotrexate with defined ratio. Biomacromolecule 13:982–991Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2018

Authors and Affiliations

  1. 1.College of PharmacyChung-Ang UniversitySeoulRepublic of Korea

Personalised recommendations