Dendrimers as biopharmaceuticals: Synthesis and properties

Current Topics in Medicinal Chemistry

Volumn 8, Issue 14, 2008, Pages 1294-1309

  Villalonga Barber, Carolina ^a   Micha Screttas, Maria ^a   Steele, Barry R ^a   Georgopolous, Aristidis ^b   Demetzos, Costas ^b  

^a INSTITUTE OF BIOLOGY   (Greece)

^b UNIVERSITY OF ATHENS   (Greece)

Author keywords

Click chemistry; Dendrimer synthesis; Double exponential synthesis; Double stage synthesis; Lego chemistry; Orthogonal coupling; Pharmacodynamics; Pharmacokinetics; Self assembly; Solid phase synthesis

Indexed keywords

ACETYLSALICYLIC ACID; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; CAMPTOTHECIN; CISPLATIN; DENDRIMER; DICLOFENAC; DIFLUNISAL; DIMETHOXYCURCUMIN; DOXORUBICIN; FLUOROURACIL; FLURBIPROFEN; GLATIRAMER; IBUPROFEN; INDOMETACIN; KETOPROFEN; METHOTREXATE; NANOCARRIER; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; PACLITAXEL; PENICILLIN G; PIROXICAM; POLYAMIDOAMINE; PROPANOL; SEVELAMER; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; CHEMICAL REACTION; CHEMICAL STRUCTURE; CLICK CHEMISTRY; DOUBLE EXPONENTIAL SYNTHESIS; DOUBLE STAGE SYNTHESIS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG ELIMINATION; DRUG FORMULATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SOLUBILITY; DRUG STRUCTURE; ENCAPSULATION; HUMAN; NONHUMAN; ORTHOGONAL COUPLING; POLYMERIZATION; PURIFICATION; REVIEW; SELF ASSEMBLY; SOLID PHASE SYNTHESIS; STRUCTURE ANALYSIS;

ANTI-BACTERIAL AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTICARCINOGENIC AGENTS; BIOLOGICAL AVAILABILITY; DENDRIMERS; DRUG DELIVERY SYSTEMS; MODELS, BIOLOGICAL;

EID: 52949152401     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802608785849012     Document Type: Review

References (105)

1. Buhleier, E.; Wehner, W.; Vögtle, F. Cascade-chain-like and nonskid-chain-like synthesis of molecular cavity topologies. Synthesis 1978, 155-158.
2. (a) Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. A new class of polymers- starburst-dendritic macromolecules. Polym. J. 1985, 17, 117-132.
3. (b) Tomalia, D. A.; Baker, H,; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. dendritic macromolecules: synthesis of starburst dendrimers. Macromolecules 1986, 19, 2466-2468.
4. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. Micelles. Part 1. cascade molecules: a new approach to micelles. A [27]-arborol. J. Org. Chem. 1985, 50, 2063-2004.
5. Fischer, M.; Vögtle, F. Dendrimers: from design to applications - a progress report. Angew. Chem. Int. Ed. 1999, 38, 884-905.
6. Brabander-van der Berg, E. M. M.; Meijer, E. W. Poly (propylene imine) dendrimers: large-scale synthesis by heterogeneously catalyzed hydrogenations. Angew. Chem. Int. Ed. 1993, 32, 1308-1310.
7. Hawker, C. J.; Fréchet, J. M., J. Preparation of polymers with controlled molecular architecture. a new convergent approach to dendritic macromolecules. J. Am. Chem. Soc. 1990, 112, 7638-7647.
8. Grayson, S. M.; Fréchet, J. M. J. Convergent dendrons and dendrimers: from synthesis to applications. Chem. Rev. 2001, 101, 3819-3867.
9. Svenson, S.; Tomalia, D.A. Dendrimers in biomedical applications - reflections on the field. Adv. Drug Deliv. Rev. 2005, 57, 2106-2129.
10. (a) Wooley, K.L.; Hawker, C. J.; Fréchet, J. M. J. Hyperbranched macromolecules via a novel double-stage convergent growth approach. J. Am. Chem. Soc. 1991, 113, 4252-4261.
11. 186 and their fluorinated analogs. J. Am. Chem. Soc. 1992, 114, 1018-1025.
12. (c) Xu, Z. F.; Kahr, M.; Walker, K. L.; Wilkins, C. L.; Moore, J. S. Phenylacetylene dendrimers by the divergent convergent and double-stage convergent methods. J. Am. Chem. Soc. 1994, 116, 4537-4550.
13. Kawaguchi, T.; Walker, K. L.; Wilkins, C. L; Moore, J. S. Double exponential dendrimer growth. J. Am. Chem. Soc. 1995, 117, 2159-2165.
14. Orthogonal strategies comprise those sets of reactions which achieve the same goal by diffeent, independent and non-conflicting routes. The term has most often been applied to independent classes of protecting groups where each class of groups can be removed in any order and in the presence of all other classes (Barany, G.; Merrifield, R. B. A New amino protecting group removable by reduction. chemistry of the dithiasuccinoyl (Dts) function. J. Am. Chem. Soc. 1977, 99, 7363-7365.
15. Spindler, R.; Frechet, J. M. J. 2-Step approach towards the accelerated synthesis of dendritic macromolecules. J. Chem. Soc. Perkin Trans. 1 1993, 913-918.
16. Zeng, F.; Zimmerman, S. C. Rapid synthesis of dendrimers by an orthogonal coupling strategy. J. Am. Chem. Soc. 1996, 118, 5326-5327.
17. (a) Deb, S. K.; Maddux, T. M.; Yu, L. A simple orthogonal approach to poly(phenylenevinylene) dendrimers. J. Am. Chem. Soc. 1997, 119, 9079-9080.
18. (b) Ishida Y.; Jikei, M.; Kakimoto, M. Rapid synthesis of aromatic polyamide dendrimers by an orthogonal and a double-stage convergent approach. Macromolecules 2000, 33, 3202-3211.
19. (c) Peerlings, H. W. I.; van Benthem, R. A. T. M.; Meijer, E. W. Fast and convenient construction of carbamate/urea-based dendrimers with a diisocyanate building block. J. Polym. Sci., A: Polym. Chem. 2001, 39, 3112-3120)
20. (d) Zang, W.; Nowlan, D.T., III, Thomson, L. M.; Lackowski, W.M.; Simanek, E. E. Orthogonal, convergent syntheses of dendrimers based on melamine with one or two unique surface sites for manipulation. J. Am. Chem. Soc. 2001, 123, 8914-8922.
21. Maraval, V.; Pyzowski, J.; Caminade, A. M; Majoral, J. P. "Lego", chemistry for the straightforward synthesis of dendrimers. J. Org. Chem. 2003, 68, 6043-6046.
22. (b) Maraval, V.; Caminade, A. M; Majoral, J. P.; Blais, J-C. Dendrimer design: how to circumvent the dilemma of a reduction of steps or an increase of function multiplicity? Angew. Chem., Int. Ed. 2003, 42, 1822-1826.
23. Maraval, V.; Laurent, R.; Marchand, P.; Caminade, A. M.; Majoral, J. P. Accelerated methods of synthesis of phosphorus-containing dendrimers. J. Organomet. Chem. 2005, 690, 2458-2471.
24. (a) Mathias, J. P.; Stoddart, F. Constructing a molecular LEGO set. Chem. Soc. Rev. 1992, 21, 215-225.
25. (b) Ashton, P. R.; Brown, G. R.; Isaacs, N. S.; Giuffrida, D.; Kohnke, F. H.; Mathias, J. P.; Slawin, A. M. Z.; Smith, D. R.; Stoddart, J. F.; Williams, D. J. Molecular LEGO. 1. Substrate-directed synthesis via stereoregular Diels-Alder oligomerizations. J. Am. Chem. Soc. 1992, 114, 6330-6353.
26. Börner, H. G. Multifuctional polymer-bioconjugates as molecular LEGO® bricks. Macromol. Chem Phys. 2007, 208, 124-130.
27. (b) Bolz, I.; May, C.; Spange, S. Solvatochromic properties of Schiff bases derived from 5-aminobarbituric acid: chromophores with hydrogen bonding pattens as components for coupled structures. New J. Chem. 2007, 31, 1568-1571.
28. Lim, J.; Simanek, E. E. Toward the next-generation drug delivery vehicle: synthesis of a dendrimer with four orthogonally reactive groups. Mol. Pharmaceutics 2005, 2, 273-277.
29. Umali, A. P.; Crampton, H. L.; Simanek, E. E. Triazine dendrimers with orthogonally protected amines on the periphery masking amines with Dde and BOC groups provides an alternative to carrying protected alcohols and disulfides through an iterative synthesis. J. Org. Chem. 2007, 72, 9866-9874.
30. Gyoal, P.; Yoon, K.; Week, M. Multifunctionalization of dendrimers through orthogonal transformations. Chem. Eur. J. 2007, 13, 8801-8810.
31. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 2001, 40, 2004-2021.
32. Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Shell, A.; Voit, B.; Pyun, J.; Fréchet, J. M. J; Sharpless, K. B.; Fokin. V. 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. 2004, 43, 3928-3932.
33. Wu, P.; Malkoch, M.; Hunt, J. N.; Vestberg, R.; Kaltgrad, E.; Finn, M. G.; Fokin, V.V.; Sharpless, K. B.; Hawker, C. J. Multivalent, bifunctional dendrimers prepared by click chemistry. Chem. Commun. 2005, 46, 5775-5777.
34. (a) Touaibia, M.; Wellens, A.; Shiao, T. C.; Wang, Q.; Sirois, S.; Bouckaert, J.; Roy, R. Mannosylated G(0) dendrimers with nanomolar affinities to Escherichia coli FimH. ChemMedChem. 2007, 8, 1190-1201.
35. (b) Dijkgraaf, I.; Rijnders, A. Y.; Soede, A.; Dechesne, A. C.; van Esse, G. W.; Brouwer, A. J.; Corstens, F. H. Boerman, O. C.; Rijkers, D. T.; Liskamp, R. M. Synthesis of DOTA-conjugated multivalent cyclic-RGD peptide dendrimers via 1,3-dipolar cycloaddition and their biological evaluation; implications for tumor targeting and tumor imaging purposes. Org. Biomol. Chem. 2007, 6, 935-944.
36. (c) Gopin, A.; Ebner, E.; Attali, B.; Shabat, D. Enzymatic activation of second-generation dendritic prodrugs: conjugation of self-immolative dendrimers with poly(ethylene glycol) via click chemistry. Bioconjug. Chem. 2006, 17, 1432-1440.
37. Ornelas, C.; Ruiz Aranzaes, J.; Clouter, E.; Alves, S.; Astruc, D. Click assembly of 1,2,3-triazole-linked dendrimers, including ferrocenyl dendrimers, which sense both oxo anions and metal cations. Angew. Chem. Int. Ed. 2007, 46, 872-877.
38. 2 and remarkable catalytic hydrogenation activity of precise Pd nanoparticles stabilized by 1,2,3-triazole-containing dendrimers. Chem. Eur. J. 2008, 14, 50-64.
39. Killops, K. L.; Luis M. Campos, L. M.; Hawker, C. J. Robust, efficient and orthogonal synthesis of dendrimers via thio1-ene "click" chemistry. J. Am. Chem. Soc. 2008, 130, 5062-5064.
40. (a) Whitesides, G. M.; Mathias, J. P.; Seto, C. T. Molecular self-assembly and nanochemistry - a chemical strategy for the synthesis of nanostructures. Science 1991, 254, 1312-1319.
41. (b) Service, R. F. How far can we push chemical self-assembly? Science 2005, 309, 95.
42. Lehn, J.-M. Supramolecular chemistry - scope and perspectives. molecules, supermolecules, and molecular devices (Nobel Lecture). Angew. Chem. Int. Ed. 1988, 27, 89-112.
43. (b) Terech, P.; Weiss, R. G. Low molecular mass gelators of organic liquids and the properties of their gels. Chem. Rev. 1997, 97, 3133-3160.
44. (c) Prins, L. J.; Timmerman, P.; Reinhoudt, D. N. Non-covalent synthesis of organic nanostructures. Pure Appl. Chem. 1998, 70, 1459-1468.
45. (d) Raymo, F. M.; Stoddart, J. F. Interlocked macromolecules. Chem. Rev. 1999, 99, 1643-1663.
46. Zimmerman S. C.; Zeng, F.; Reichert D. E.; Kolotuchin, S. V. Self-assembling dendrimers. Science 1996, 271, 1095-1098.
47. Numata, M.; Ikeda, A.; Shinkai, S. Properly assembled dendrons can be immobilized into dendrimers by in situ cross-link. Chem. Lett. 2000, 370-371.
48. Corbin, P. S.; Lawless, L. J.; Li, Z.; Ma, Y.; Witmer, M. J.; Zimmerman, S. C. Discrete and polymeric self-assembly dendrimers: hydrogen bond-mediated assembly with high stability and high fidelity Proc. Natl. Acad. Sci. USA 2002, 99, 5099-5104.
49. Nilsen, T. W.; Grayzel, J.; Prensky, W. Dendritic nucleic acid structures. J. Theor. Biol. 1997, 187, 273-284.
50. Li, Y.; Tseng, Y. D.; Kwon, S. Y.; D'Espaux, L.; Bunch, J. S.; McEuen, P. L.; Luo, D. Controlled assembly of dendrimer-like DNA. Nat. Mater. 2004, 3, 38-42.
51. Klimash, J. W.; Brothers, H. M., II; Swanson, D. R.; Yin, R.; Spindler, R.; Tomalia, D. A.; Hsu, Y.; Cheng, R. C. Disulfide-containing dendritic polymers. U.S. Patent 6,020,457, February 1, 2000.
52. (a) Loweth, C. J.; Caldwell,,W. B.; Peng, X.; Alivisatos, A. P.; Schultz, P. G. DNA-based assembly of gold nanocrystals Angew. Chem. Int. Ed. 1999, 38, 1808-1812.
53. (b) Willner, I.; Patolsky, F.; Wasseman, J. Photoelectrochemistry with controlled DNA-cross-linked CdS nanoparticle arrays. Angew. Chem. Int. Ed. 2001, 40, 1861-1864.
54. DeMattei, C. R.; Huang, B.; Tomalia, D. A. Designed dendrimer syntheses by self-assembly of single-site, ssDNA functionalized dendrons. Nano Lett. 2004, 4, 771-777.
55. Choi, Y.; Mecke, A.; Orr, B. G.; Banaszack Holl, M; M.;, Baker, J. R., Jr. DNA-directed synthesis of Generation 7 and 5 PAMAM dendrimer nanoclusters. Nano Lett. 2004, 4, 391-397.
56. Choi, Y.; Thomas, T.; Kotlyar, A.; Islam, M.T.; Baker, J. R., Jr. Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. Chem. Biol. 2005, 12, 35-43.
57. (a) Fant, K.; Esbjörner, E. K.; Lincoln, P.; Nordèn, B.; DNA condensation by PAMAM dendrimers: self-assembly characteristics and effect on transcription. Biochemistry 2008, 47, 1732-1740.
58. (b) Lim, Y. B.; Lee, E.; Lee, M. Controlled bioactive nanostructures. from self-assembly of peptide building blocks. Angew. Chem. Int. Ed. 2007, 46, 9011-9014.
59. Joukheijm, P.; van der Schoot, P.; Schenning, A. P. H. J.; Meijer, E. W. Probing the solvent-assisted nucleation pathway in chemical self-assembly. Science 2006, 313, 80-83.
60. Lobse, B.; Ivanov, M. T.; Andreasen, J. W.; Vestberg, R.; Hvilsted, S.; Berg, R. H.; Ramanujam, P. S.; Hawker, C. J.; Mortensen, K. Self-assembly of urach-PAMAM dendrimer systems into domains of micrometer length scale. Macromolecules 2007, 40, 1779-1781.
61. Hahn, U.; Cardinali, F.; Nierengarten, J.F. Supramolecular chemistry for the self-assembly of fullerene-rich dendrimers. New J. Chem. 2007, 31, 1128-1138.
62. Fernández, G.; Perez, E. M.; Sánchez, L.; Martin, N. An electroactive dynamically polydisperse supramolecular dendrimer. J. Am. Chem. Soc. 2008, 130, 2410-2411.
63. Clark, C. G., Jr.; Wenzel, R. J.; Andreitchenko, E. V.; Steffen, W.; Zenobi, R.; Müllen, K. Controlled megaDalton assembly with locally stiff but globally flexible polyphenylene dendrimers. J. Am. Chem. Soc. 2007, 129, 3292-3301.
64. (a) Kikkeri, R.; Hossain, L.H.; Seeberger, P.H. Supramolecular onepot approach to fluorescent glycodendrimers. Chem. Commun. 2008, DOI: 10.1039/b802177e.
65. (b) Gottschaldt, M.; Koth, D,; Muller, D.; Klette, I,; Rau, S.; Gorls,, H.;. Schafer, B.; Baum, R. P.; Yano, S. Synthesis and strudture of novel sugar-substituted bipyridine complexes of rhenium and 99m-technetium. Chem. Eur. J. 2007, 13, 10273-10280.
66. (c) Roy, R.; Kim, J. M. Cu(II)-self-assembling bipyridyl-glycoclusters and dendrimers bearing the Tn-antigen cancer marker: syntheses and lectin binding properties. Tetrahedron 2003, 59, 3881-3892.
67. Dahan, A.; Portnoy, M. Dendrons and dendritic catalysts immobilized on solid support: synthesis and dendritic effects in catalysis. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 235-262.
68. Cui-Fen, L.; Cheng, X.; Zu-Xing, C.; Gui-Chun, Y. Synthesis and investigation of PEG-supported amino dendrimers. React. Funct. Polym. 2006, 66, 952-956.
69. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149-2154;
70. Merrifield, R. B. Automated synthesis of peptides. Science 1965, 150, 178-185.
71. Früchtel, J. S.; Jung, G. Organic chemistry on solid supports. Angew. Chem. Int. Ed. 1996, 35, 17-42.
72. Swali, V.; Wells, N. J.; Langley, J.; Bradley, M. Solid-phase dendrimer synthesis and the generation of super-high-loading resin beads for combinatorial chemistry. J. Org. Chem. 1997, 62, 4902-4903.
73. (a) Hudson, R. H. E.; Damha, M. Nucleic acid dendrimers: novel biopolymer structures. J. Am. Chem., Soc. 1993, 115, 2119-2124;
74. (b) Hudson, R. H. E.; Robidoux, S.; Damha, M. Divergent solid-phase synthesis of nucleic acid dendrimers. Tetrahedron Lett. 1998, 39, 1299-1302.
75. Bharathi, P.; Patel, U.; Kawaguchi, T.; Pesak, D. J.; Moore, J. S. Improvements in the synthesis of phenylacetylene monodendrons including a solid-phase convergent method. Macromolecules 1995, 28, 5955-5963.
76. Dilly, S. J.; Carlisle, S. J.; Clark, A. J.; Shepherd, A. R.; Smith, S. C.; Taylor, P. C.; Marsh, A. Practical syntheses of [1,2,5,]-triazine dendriiic molecules on solid supports. J. Polym. Sci. Part A: Polym. Chem. 2006, 44, 2249-2259.
77. (a) Clouet, A.; Darbre, T.; Reymond, J. L. Combinatorial synthesis, selection, and properties of esterase peptide dendrimers. Biopolymers 2006, 84, 114-123.
78. (b) Kaneshiro, T. L.; Wang, X.; Lu, Z. R. Synthesis, characterization, and gene delivery of poly-lysine octa(3-aminopropyl)silsesquioxane dendrimers: nanoglobular drug carriers with precisely defined molecular architectures. Mol. Pharmaceutics 2007, 4, 759-768.
79. (c) Xu, H.; Regino, C. A.; Bernardo, M.; Koyama, Y.; Kobayashi, H.; Choyke, P. L.; Brechbiel, M. W. Toward improved syntheses of dendrimer-based magnetic resonance imaging contrast agents: new bifunctional diethylenetriaminepentaacetic acid ligands and nonaqueous conjugation chemistry. J. Med. Chem. 2007, 50, 3185-3193.
80. (d) Touaibia, M.; Roy, R. Glycodendrimers as anti-adhesion drugs against type 1 Fimbriated E-Coli Uropathogcnic Infections Mini-Rev. Med. Chem. 2007, 7, 1270-1283.
81. Hermkens, P. H. H.; Ottenheijm, H. C J.; Rees, D. Solid-phase organic reactions: a review of the recent literature. Tetrahedron 1996, 52, 4527-4554.
82. Bayer, E. Towards the Chemical Synthesis of Proteins. Angew. Chem. Int. Ed. 1991, 30, 113-129;
83. Kempe, M.; Barany, G. CLEAR: a novel family of highly cross-linked polymeric supports for solid-phase peptide synthesis. J. Am. Chem. Soc. 1996, 118, 7083-7093.
84. Tam, J.P. Synthetic peptide vaccine design - synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 5409-5413.
85. 3 isocyanate-type monomers. Tetrahedron 2003, 59, 3945-3953.
86. (a) Bradley, M. High-loading resin beads for solid phase synthesis using branching symmetrical dendrimers. Chem. Commun. 2000, 293-284.
87. (b) Dahan, A.; Portnoy, M. Pd catalysis on dendronized solid support: generation effects and the influence of the backbone structure. J. Am. Chem. Soc., 2007, 129, 5860-5869;
88. (c) Kehat, T.; Goren, K.; Portnoy, M. Dendrons on insoluble supports: synthesis and applications. New J. Chem. 2007, 31, 1218-1242.
89. Devalapally, H.; Chakilam, A.; Amiji, M. M. Role of nanotechnology in pharmaceutical product development. J. Pharm. Sci. 2007, 96, 2547-2565.
90. Demetzos, C. Dendrimers as drug carriers. A new approach to increase the potential of bioactive natural products. Nat. Prod. Commun. 2006, 1, 593-600.
91. Yang, H.; Kan, W. J. Dendrimers for pharmaceutical and biomedical applications. J. Biomater. Sci. Polym. Ed. 2006, 17, 3-19.
92. Gupta, U.; Agashe, H. B.; Asthana, A.; Jain, N. K. Dendrimers: novel polymeric nanoarchitectures for solubility enhancement. Biomacromol. 2006, 7, 649-658.
93. Bai, S.; Thomas, C.; Rawat A.; Ahsan, F. Recent progress in dendrimer-based nanocarriers. Crit. Rev. Ther. Drug Carrier Syst. 2006, 23, 437-495.
94. 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. 2008, DOI: 10.1016/ j.ejmech.2007.12.021.
95. D'Emanuele, A.; Attwood; D. Dendrimer-drug interactions. Adv. Drug Deliv. Rev. 2005, 57, 2147-2162.
96. Chauhan, A. S.; Srideve, S,; Chalasani, K. B.; Jain, A. K.; Jain, S. K.; Jain, N: K.; Diwan, P. V. Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin. J. Control. Release 2003, 90, 335-343.
97. Chauhan, A. S.; Jain, N. K.; Diwan, P. V.; Khopade, A. J. Solubility enhancement of indomethacin with poly(amidoamine) dendrimers and targeting to inflammatory regions of arthritic rats. J. Drug Target. 2004, 12, 575-583.
98. Markatou, E.; Gionis, V.; Chryssikos, G. D.; Hatziantoniou, S.; Georgopoulos, A.; Demetzos, C. Molecular interactions between dimethoxycurcumin and PAMAM dendrimer carriers. Int. J. Pharm. 2007, 339, 231-236.
99. Papagiannaros, A.; Dimas, K.; Papaioannou, G. T.; Demetzos, C. Doxorubicin-PAMAM dendrimer complex attached to liposomes: cytotoxic studies against human cancer cell lines. Int. J. Pharm. 2005, 302, 29-38.
100. Papagiannaros, A.; Demetzos, C. Release advantages of a liposomal dendrimer-doxorubicin complex over conventional lipogomal formulation of doxorubicin. In Nanomaterials and Nanosystems for Biomedical Applications; Mozafari, M.R.; Ed.; Springer; 2004; pp. 135-144.
101. Ooya, T.; Lee, J.; Park, K. Effects of ethylene glycol-based graft, star-shaped, and dendritic polymers on solubilization and controlled release of paclitaxel. J. Control. Release 2003, 93, 121-127.
102. Malik, N.; Evagorou, E.G.; Duncan, R. Dendrimer-platinate: a novel approach to cancer chemotherapy. Anticancer Drugs 1999, 10, 767-776.
103. Quintana, A.; Raczka, E.; Pichler, L.; Lee, I.; Myc, A.; Majoros, I.; Patri, A. K; Thomas, T.; Mule, J.; Baker, J. R., Jr. Design and function of a dendrimer based therapeutic nanodevice targeted to tumor cells through the folate receptor. Pharm. Res. 2002, 19, 1310-1316.
104. Ke, W.; Zhao, Y.; Huang, R.; Jiang, C.; Pei, Y. Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system. J. Pharm. Sci. 2008, 97, 2208-2216.
105. D'Emmanuele, A.; Jevprasesphant, R.; Penny, J.; Attwood, D. The use of a dendrimer propanolol prodrug to bypass efflux transporters and enhance oral bioavailability. J. Control. Release 2004, 95, 447-453.