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96 8 Dendrimeric Libraries
Dendrimeric peptide inhibitors of human papillomaviruses infectivity were
identified by minilibrary approach [10].
N-linked glycopeptides are available via solid-phase aspartylation [6]. This
aspartylation will have far-reaching applications in the syntheses of N-linked
glycopeptides and N-linked glycopeptide libraries.
OBOC glycopeptide dendrimer library with 65,536 members was tested for
binding of Jurkat cells [18]. The identified dendrimer—(ˇ-Gal-Gly-Arg-His-Ala)
2
-
Dap-Thr-Arg-His-Asp-Cys-NH
2
—and its derivatives are efficient delivery vehicles.
Its colchicine conjugate was cytotoxic with LD
50
1.5 M, whereas the pen-
tagalactosylated dendrimer—ˇ-Gal
4
-(Lys-Arg-His-Leu)
2
-Dap-Thr-Tyr-His-Lys(ˇ-
Gal)-Cys-OH—selectively labels Jurkat cells, but its colchicine conjugate was
not cytotoxic. Tubulin-binding assays demonstrated that the colchicine had to be
released as the active drug.
References
1. Banik, J., Brady, S.: Cloning and characterization of new glycopeptide gene clusters found in
an environmental DNAmegalibrary. Proc. Natl. Acad. Sci. USA 105(45), 17273–17277 (2008)
2. Bergeron-Brlek, M., Shiao, T.C., Trono, M.C., Roy, R.: Synthesis of a small library of bivalent
˛-D-mannopyranosides for lectin cross-linking. Carbohydr. Res. 346(12), 1479–1489 (2011)
3. Biswas, R., Maillard, N., Kofoed, J., Reymond, J.L.: Comparing dendritic with linear esterase
peptides by screening spot arrays for catalysis. Chem. Commun. 46, 8746–8748 (2010)
4. Carnall, J., Waudby, C., Belenguer, A., Stuart, M., Peyralans, J.P., Otto, S.: Mechanosensitive
self-replication driven by self-organization. Science 327(5972), 1502–1506 (2010)
5. Chabre, Y., Roy, R.: Design and creativity in synthesis of multivalent neoglycoconjugates. Adv.
Carbohydr. Chem. Biochem. 63, 165–393 (2010)
6. Conroy, T., Jolliffe, K.A., Payne, R.J.: Synthesis of N-linked glycopeptides via solid-phase
aspartylation. Org. Biomol. Chem. 8, 3723–3733 (2010)
7. Cougnon, F.B.L., Sanders, J.K.M.: Evolution of dynamic combinatorial chemistry. Acc. Chem.
Res. (in press). doi: 10.1021/ar200240m
8. Darbre, T., Reymond, J.L.: Peptide dendrimers as artificial enzymes, receptors, and drug-
delivery agents. Acc. Chem. Res. 39(12), 925–934 (2006)
9. Darbre, T., Reymond, J.L.: Glycopeptide dendrimers for biomedical applications. Curr. Top.
Med. Chem. 8(14), 1286–1293 (2008)
10. Donalisio, M., Rusnati, M., Civra, A., Bugatti, A., Allemand, D., Pirri, G., Giuliani, A.,
Landolfo, S., Lembo, D.: Identification of a dendrimeric heparan sulfate-binding peptide that
inhibits infectivity of genital types of humanpapillomaviruses. Antimicrob.Agents Chemother.
54(10), 4290–4299 (2010)
11. Dulery, V., Renaudet, O., Wilczewski, M., Van Der Heyden, A., Labbe, P., Dumy, P.:
Randomized combinatorial library of heteroglycoclusters (hgc). J. Comb. Chem. 10(3), 368–
371 (2008)
12. Durai, C.R.S., Harding, M.M.: Targeting nucleic acids using dynamic combinatorial chemistry.
Aust. J. Chem. 64(6), 671–680 (2011)
13. Fukuda, T., Onogi, S., Miura, Y.: Dendritic sugar-microarrays by click chemistry. Thin Solid
Films 518(2, Sp. Iss. SI), 880–888 (2009)
14. Hojo, H., Nakahara, Y.: Recent progress in the field of glycopeptide synthesis. Biopolymers
88(2), 308–324 (2007)
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References 97
15. Huc, I., Nguyen, R.: Dynamic combinatorial chemistry. Comb. Chem. High Through Screen.
4(1), 53–74 (2001)
16. Hunt, R.A.R., Otto, S.: Dynamic combinatorial libraries: new opportunities in systems
chemistry. Chem. Commun. 47, 847–858 (2011)
17. Johansson, E., Crusz, S., Kolomiets, E., Buts, L., Kadam, R., Cacciarini, M., Bartels, K.M.,
Diggle, S., Camara, M., Williams,P., Loris, R.,Nativi, C.,Rosenau, F., Jaeger, K.E., Darbre, T.,
Reymond, J.L.: Inhibitionand dispersion of Pseudomonas aeruginosa biofilms by glycopeptide
dendrimers targeting the fucose-specific lectin lecB. Chem. Biol. 15(12), 1249–1257 (2008)
18. Johansson, E.M.V., Dubois, J., Darbre, T., Reymond, J.L.: Glycopeptide dendrimer colchicine
conjugates targeting cancer cells. Bioorg. Med. Chem. 18(17), 6589–6597 (2010)
19. Johansson, E., Kolomiets, E., Rosenau, F., Jaeger, K.E., Darbre, T., Reymond, J.L.: Combina-
torial variation of branching length and multivalency in a large (390 625 member) glycopeptide
dendrimer library: ligands for fucose-specific lectins. New J. Chem. 31(7), 1291–1299 (2007)
20. Kikkeri, R., Gruenstein, D., Seeberger, P.H.: Lectin biosensing using digital analysis of Ru(II)-
glycodendrimers. J. Am. Chem. Soc. 132(30), 10,230–10,232 (2010)
21. Kolomiets, E., Johansson, E., Renaudet, O., Darbre, T., Reymond, J.L.: Neoglycopeptide
dendrimer libraries as a source of lectin binding ligands. Org. Lett. 9(8), 1465–1468 (2007)
22. Kolomiets, E., Swiderska, M., Kadam, R., Johansson, E., Jaeger, K.E., Darbre, T., Reymond,
J.L.: Glycopeptide dendrimers with high affinity for the fucose-binding lectin LecB from
Pseudomonas aeruginosa. ChemMedChem 4(4), 562–569 (2009)
23. Macmillan, D.,Daines, A.:Recent developments in the synthesis and discovery of oligosaccha-
rides and glycoconjugates for the treatment of disease. Curr. Med. Chem. 10(24), 2733–2773
(2003)
24. Maillard, N., Clouet, A., Darbre, T., Reymond, J.L.: Combinatorial libraries of peptide
dendrimers: design, synthesis, on-bead high-throughput screening, bead decoding and char-
acterization. Nat. Protocol. 4(2), 132–142 (2009)
25. Maljaars, C., Andre, S., Halkes, K., Gabius, H.J., Kamerling, J.: Assessing the inhibitory
potency of galectin ligands identified from combinatorial (glyco)peptide libraries using surface
plasmon resonance spectroscopy. Anal. Biochem. 378(2), 190–196 (2008)
26. Meldal, M., Tornoe, C., Nielsen, T., Diness, F., Le Quement, S., Christensen, C., Jensen,
J., Worm-Leonhard, K., Groth, T., Bouakaz, L., Wu, B., Hagel, G., Keinicke, L.: Ralph
F. Hirschmann award address 2009: Merger of organic chemistry with peptide diversity.
Biopolymers 94(2), 161–182 (2010)
27. Meyer, C., Joiner, C., Stoddart, J.: Template-directed synthesis employing reversible imine
bond formation. Chem. Soc. Rev. 36(11), 1705–1723 (2007)
28. Moulin, E., Cormos, G., Giuseppone, N.: Dynamic combinatorial chemistry as a tool for the
design of functional materials and devices. Chem. Soc. Rev. 41, 1031–1049 (2012)
29. Murase, T., Tsuji, T., Kajihara, Y.: Efficient and systematic synthesis of a small glycoconjugate
library having human complex type oligosaccharides. Carbohydr. Res. 344(6), 762–770 (2009)
30. Nestler, H.: Combinatorial chemistry and fragment screening—two unlike siblings? Curr. Drug
Discov. Technol. 2(1), 1–12 (2005)
31. Niederhafner, P., Sebestik, J., Jezek, J.: Glycopeptide dendrimers, Part II. J. Pept. Sci. 14(1),
44–65 (2008)
32. Pourceau, G., Meyer, A., Vasseur, J.J., Morvan, F.: Combinatorial and automated synthesis of
phosphodiester galactosyl cluster on solid support by click chemistry assisted by microwaves.
J. Org. Chem. 73(15), 6014–6017 (2008)
33. Renaudet, O.: Recent advances on cyclopeptide-based glycoclusters. Mini. Rev. Org. Chem.
5(4), 274–286 (2008)
34. Reymond, J.L., Darbre, T.: Peptide and glycopeptide dendrimer apple trees as enzyme models
and for biomedical applications. Org. Biomol. Chem. 10, 1483–1492 (2012)
35. 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)
98 8 Dendrimeric Libraries
36. Roy, R.: A decade of glycodendrimer chemistry. Trends Glycosci. Glycotechnol. 15(85),
291–310 (2003)
37. Roy, R., Touaibia, M.: Carbohydrate-Protein and Carbohydrate-Carbohydrate Interactions;
Comprehensive Glycoscience. Application of Multivalent Mannosylated Dendrimers in Gly-
cobiology, pp. 821–870. Elsevier, Utrecht (2007)
38. Ruff, Y., Buhler, E., Candau, S.J., Kesselman, E., Talmon, Y., Lehn, J.M.: Glycodynamers:
Dynamic polymers bearing oligosaccharides residues—generation, structure, physicochemi-
cal, component exchange, and lectin binding properties. J. Am. Chem. Soc. 132(8), 2573–2584
(2010)
39. 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)
40. Shin, D.S., Kim, D.H., Chung, W.J., Lee, Y.S.: Combinatorial solid phase peptide synthesis
and bioassays. J. Biochem. Mol. Biol. 38(5), 517–525 (2005)
41. Xian, M., Fatima, Z., Zhang, W., Fang, J., Li, H., Pei, D., Loo, J., Stevenson, T., Wang, P.:
Identification of ˛-galactosyl epitope mimetics through rapid generation and screening of
C-linked glycopeptide library. J. Comb. Chem. 6(1), 126–134 (2004)
42. Yang, S., Coles, D., Esposito, A., Mitchell, D., Toth, I., Minchin, R.: Cellular uptake of self-
assembled cationic peptide-DNA complexes: multifunctional role of the enhancer chloroquine.
J. Control. Rel. 135(2), 159–165 (2009)
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Chapter 9
Dendrimers in Catalysis
Dendrimer-encapsulated nanoparticles play a role of excellent catalysts for both
homogeneous and heterogeneous catalysis [2, 21]. In catalytic applications, den-
drimers serve as catalytically active species and/or soluble supports for catalytically
active species [17, 18, 20]. Due to nanosize dimensions, dendrimers resemble
biologically active enzymes with a little bit lower efficacy.
Small increments of free activation enthalpy govern enantioselectivity in a
reaction. Thus, these transformations are in general suited for assessing “den-
dritic effects” which result from the immobilization of molecular catalysts. Chiral
dendrimer catalysts are extremely selective due to a high level of molecular
monodispersity, structural regularity, and well-defined catalytic sites. They were
synthesized either by immobilization of chiral catalysts to achiral dendrimers or
by attachment of achiral complexes to chiral dendrimer structures. The topic of
stereoselective dendrimer catalysis was reviewed [10].
The combination of theadvantages of both homogeneous and heterogeneous sys-
tems can serve as a Holy Grail of catalysis. Nanoparticles are leading heterogeneous
catalysts with divergent reactivity and selectivity. A modification of heterogeneous
platinum nanoparticles which can catalyze typical homogeneous catalytic reactions
was described [24]. Platinum nanoparticles were selectively oxidized by the hyper-
valent iodine species PhICl
2
and catalyzed a range -bond activation reactions.
This modification of nanoparticles can serve for further development of reactions
previously inaccessible in heterogeneous catalysis.
Chiral amphiphilic G1–G3 dendritic organocatalysts were synthesized [15]. Due
to the presence of an optically active polar proline-derived core and nonpolar
hydrocarbon dendrons, the organocatalysts were effective for the asymmetric aldol
and nitro-Michael additionsin oil-in-wateremulsions. Larger hydrophobicdendrons
improved the reaction enantioselectivity, promoted emulsion formation in water,
decreased catalyst loading (to 1 mol%), and facilitated catalyst recovery after the
reactions. On the other hand, larger dendrons increased the steric hindrance and
lower catalytic activity. However, some of the G1- and G2-hindered dendritic
organocatalysts possessed better catalytic activity. The dendritic catalysts can be
J.
ˇ
Sebest
´
ık et al., Biomedical Applications of Peptide-, Glyco- and Glycopeptide
Dendrimers, and Analogous Dendrimeric Structures,
DOI 10.1007/978-3-7091-1206-9
99
9, © Springer-Verlag Wien 2012
100 9 Dendrimers in Catalysis
recycled up to 5 times with negligiblelost of product yield and enantiomeric excess.
Moreover, cross contamination was not detectable even when the recovered G3
catalyst was reused in another reaction with different substrates.
A photooxidation of thioanisole by catalytically generated singlet oxygen (
1
O
2
)
was reported [8]. As a catalyst, nanodevices with approximately 30 units of
buckminsterfullerene (C
60
) bound to a G4 PAMAM dendrimer was used. The
reactivity was accelerated in aqueous solution, because improved diffusion of
hydrophobic reactant molecules into dendrimer cavities.
As potential candidates for asymmetric or micellar catalysis, phosphorous
glycodendrimers with hydrazone and xylose units have been studied [6]. These
dendrimers can be both amphiphilic or hydrophobic according to end groups on
shell sugar moieties.
Click nonaxylose dendrimers stabilized platinum nanoparticles and were catalyt-
ically active in olefin hydrogenation in water at room temperature [5]. Stabilizing
Si-based dendrimers were prepared from cheap sugar—xylose—which is produced
from corn. Water solubility of dendrimers and stabilized nanoparticles moved the
olefin hydrogenationto neat aqueous environment without a requirement of organic
cosolvents. The entire process became more “eco-friendly.”
PPI dendrimers and hyperbranched PEIs were studied for copper-catalyzed
hydrosilylation of acetophenone as soluble supports of carbo-BINAP ligands [11].
Whereas the PPI dendrimer contained up to 64 BINAP ligands per molecule, the
hyperbranchedPEI can have on average 9, 26, and 138 glutaroyl-AMINAPor carbo-
BINAP ligands. The immobilized BINAP was recycled many times without any
observable loss of activity or enantioselectivity.
Metal complexes of dendrimers were also used as catalystsfor Wacker oxidation,
hydroformylation, hydroxylation of aromatics, 2-naphthol coupling, and oxidative
coupling of styrenes and benzene [9].
The 65,536-member library of peptide dendrimers was tested as hydrolytic
catalyst of the fluorogenic substrate 1-butyryloxy-pyrene-2,7,8-trisulfonate and its
derivatives [16]. Histidine catalytic activity at the dendrimer core was attenuated by
anionic glutamate residues in the outer dendrimer branches.
The efficacy of artificial esterases based on polyhistidine peptides and polyhisti-
dine peptide dendrimers was evaluated [3]. These catalysts provided cooperativity
between multiple histidine imidazoles for binding and catalysis. The multivalent
effects of hydrolysis—common property of peptide dendrimers—wasalso observed
for linear peptides. Pre-equilibrium substrate binding was observed for the his-
tidine tripeptide and longer oligomers. These electrostatic interactions multiplied
the catalytic activity more than two orders of magnitude in comparison to reference
molecule—4-methyl imidazole. The imidazole groups of the artificial esterases can
act both as a nucleophile and general base. For 15 histidine units, dendrimeric
esterases were approximately one order of magnitude more powerful than the linear
equivalent. Further increasing of number of histidines did not provide a significant
improvement of efficacy.
G4 hydroxyl-terminated PAMAM dendrimers were used as a template for
synthesis of well-defined platinum catalysts dispersed in homemade silica
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References 101
gel [1]. Nanoparticles with 40 Pt atoms served as an efficient catalyst for alkene
isomerization from trans to cis isomers. Prior to this conversion, the nanoparticles
have to be activated with H
2
.
Transition metal nanoparticle catalysis in green solvents was reviewed [25].
Different sorts of dendrimers and their applications as homogeneous, heteroge-
neous, and solid-supported dendrimer catalysts were also reviewed [13]. For more
details about use of dendrons and dendrimers in catalysis, see [2,4, 7,10, 12,14, 15,
18–20,22, 23].
References
1. Albiter, M.A., Morales, R., Zaera, F.: Dendrimer-based synthesis of pt catalysts for hydrocar-
bon conversion. Appl. Catal. A 391(1–2), 386–393 (2011)
2. Astruc, D., Ornelas, C., Diallo, A.K., Ruiz, J.: Extremely efficient catalysis of carbon-carbon
bond formation using “click” dendrimer-stabilized palladium nanoparticles. Molecules 15(7),
4947–4960 (2010)
3. Biswas, R., Maillard, N., Kofoed, J., Reymond, J.L.: Comparing dendritic with linear esterase
peptides by screening spot arrays for catalysis. Chem. Commun. 46, 8746–8748 (2010)
4. Dahan, A., Portnoy, M.: Dendrons and dendritic catalysts immobilized on solid support:
synthesis and dendritic effects in catalysis. J. Polym. Sci. A 43(2), 235–262 (2005)
5. Gatard, S., Liang, L., Salmon, L., Ruiz, J., Astruc, D., Bouquillon, S.: Water-soluble glycoden-
drimers: synthesis and stabilization of catalytically active Pd and Pt nanoparticles. Tetrahedron
Lett. 52(16), 1842–1846 (2011)
6. Hadad, C., Majoral, J.P., Muzart, J., Caminade, A.M., Bouquillon, S.: First phosphorous
d-xylose-derived glycodendrimers. Tetrahedron Lett. 50(17), 1902–1905 (2009)
7. Helms, B., Frechet, J.: The dendrimer effect in homogeneous catalysis. Adv. Synth. Catal.
348(10–11), 1125–1148 (2006)
8. Jensen, A., Maru, B., Zhang, X., Mohanty, D., Fahlman, B., Swanson, D., Tomalia, D.:
Preparation of fullerene-shell dendrimer-core nanoconjugates. Nano Lett. 5(6), 1171–1173
(2005)
9. Karakhanov, E., Maksimov, A., Runova, E., Kardasheva, Y., Terenina, M., Kardashev, S.,
Skorkin, V., Karapetyan, L., Talanova, M.: Design of supramolecular metal complex catalytic
systems for petrochemical and organic synthesis. Russ. Chem. Bull. 57(4), 780–792 (2008)
10. Kassube, J., Gade, L.: Stereoselective dendrimer catalysis. Top. Organometal. Chem. 20,
61–96 (2006)
11. Kassube, J., Wadepohl, H., Gade, L.: Immobilisation of the binap ligand on dendrimers and
hyper-branched polymers: dependence of thecatalytic properties on the linker unit. Adv.Synth.
Catal. 351(4), 607–616 (2009)
12. Kehat, T., Goren, K., Portnoy, M.: Dendrons on insoluble supports: synthesis and applications.
New J. Chem. 31(7), 1218–1242 (2007)
13. King, A.S.H., Twyman, L.J.: Heterogeneous and solid supported dendrimer catalysts. J. Chem.
Soc. Perkin. Trans. (20), 2209–2218 (2002)
14. Liang, C., Frechet, J.: Applying key concepts from nature: transition state stabilization, pre-
concentration and cooperativity effects in dendritic biomimetics. Prog. Polym. Sci. 30(3–4),
385–402 (2005)
15. Lo, C.M., Chow, H.F.: Structural effects on the catalytic, emulsifying, and recycling properties
of chiral amphiphilic dendritic organocatalysts. J. Org. Chem. 74(15), 5181–5191 (2009)
16. Maillard, N., Darbre, T., Reymond, J.L.: Identification of catalytic peptide dendrimers by “off-
bead” in silica high-throughput screening of combinatorial libraries. J. Comb. Chem. 11(4),
667–675 (2009)
102 9 Dendrimers in Catalysis
17. Newkome, G., Shreiner, C.: Poly(amidoamine), polypropylenimine, and related dendrimers
and dendrons possessing different 1 ! 2 branching motifs: an overview of the divergent
procedures. Polymer 49(1), 1–173 (2008)
18. Newkome, G.R., Shreiner, C.: Dendrimers derived from 1 ! 3 branching motifs. Chem. Rev.
110(10), 6338–6442 (2010)
19. Niederhafner, P., Sebestik, J., Jezek, J.: Glycopeptide dendrimers. Part II. J. Pept. Sci. 14(1),
44–65 (2008)
20. Scholl, M., Kadlecova, Z.,Klok, H.A.: Dendritic and hyperbranched polyamides. Prog. Polym.
Sci. 34(1), 24–61 (2009)
21. 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)
22. Svenson, S.: Dendrimers. Kirk-Othmer Encyclop. Chem. Technol. 26, 786–812 (2007)
23. Van Dongen, S., De Hoog, H.P., Peters, R., Nallani, M., Nolte, R., Van Hest, J.: Biohybrid
polymer capsules. Chem. Rev. 109(11), 6212–6274 (2009)
24. Witham, C., Huang, W., Tsung, C.K., Kuhn, J., Somorjai, G., Toste, F.: Converting homoge-
neous to heterogeneous in electrophilic catalysis using monodisperse metal nanoparticles. Nat.
Chem. 2(1), 36–41 (2010)
25. Yan, N., Xiao, C., Kou, Y.: Transition metal nanoparticle catalysis in green solvents. Coord.
Chem. Rev. 254(9–10, SI), 1179–1218 (2010)
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Part II
Dendrimers and Their Biological
and Therapeutic Applications
Since particular dendrimeric structures are frequently designed and synthesized
with a respect to their potential biological use, their biological functions have
been touched in previous chapters primarily dedicated to their synthesis, structure,
and physicochemical features. In the following chapters, the potential biological
applications are discussed from the point of view of particular diseases and/or
utilizations. Indeed, glyco- and glycopeptide dendrimers represent coding systems
with extremely high density that can display enormous functional variability. The
introduction of modern strategies of convergent glycodendrimer synthesis has led
to immense growth of important discoveries. This paves the avenue for their appli-
cations as anticancer, antimicrobial, antiprion, and antiviral agents. They have been
used as important tools in many novel techniques and biological applications, such
as contrast agents for molecular imaging; drug and gene delivery; solubilization
effect on drugs. They can serve as active components of novel vaccines, such as of
tailor-made anticancer synthetic vaccines based on combination of small targeting
peptides or tumor-associated antigens with dendrimeric cargos. Last but not least,
neurodegenerative disorders (Alzheimer’s disease and prion-caused diseases) seem
to be inhibited with cationic glycodendrimers.
Chapter 10
Dendrimers and Solubility
Hydrophobicity of drugs and bioactive compounds reduces their solubility in water
and significantlydiminishes their activity in vivo [21]. Only 60 % of drug candidates
reach the patients, whereas the remaining 40 % of compoundsare eliminated during
the screening owing to their low water solubility, poor bioavailability, and low
permeability through biological membranes [1,14,22–25]. Therefore, a fundamental
task of drug delivery is a thorough understanding of solubility enhancement.
Dendrimers are a novel type of materials with a unique structure and properties
which are suitable for drug delivery and solubilization.
Solubilization facilitated by dendrimers is achieved by ionic interactions, hydro-
gen bonding, and hydrophobic interactions. Dendrimers can have hydrophobic
interior responsible for encapsulation of hydrophobic drugs and dendrimers can
be covered by hydrophilic shell (e.g., carbohydrates) involved in interactions with
water and solubilization [14, 22–24]. Modes of solubilizations are simple encapsu-
lation (10, 11), covalent conjugation (12, 13, 14, 16), or electrostatic interaction
(15, 16)(Fig.10.1)[21]. Dendrimer-based drug delivery not only improves the
drug bioavailability, but also it provides protection of drugs against enzymatic or
hydrolytic breakdown in vivo [23,24,26].
Dendrimers were appliedas solubilizers of variousdrugs [21], such as anticancer
drugs (camptothecin, carboplatin, chlorambucil, cisplatin, dimethoxycurcumin,
doxorubicin, etoposide, 5-fluorouracil, methotrexate, oxaliplatin, and paclitaxel),
antidepressants (venlafaxine), antifungal drugs (amphotericin B), antihemorrhagic
drugs (nimodipine), antihistaminics (famotidine), anti-inflammatory drugs
(diclofenac, diflunisal, ibuprofen, indomethacin, ketoprofen, mefenamic acid,
methylprednisolone, naproxen, nifedipine, phenylbutazone, and piroxicam),
and antimicrobial drugs (artemether, niclosamide, nadifloxacin, penicillin V,
prulifloxacin, and sulfamethoxazole).
For instance, piroxicam-loaded G3 and G4 PAMAM dendrimers enhanced the
drug solubility 107 and 222 times, respectively [19]. The half-life of elimination of
the piroxicam conjugate was significantly higher than that of pure drug. G4-based
conjugates were superior to G3 as well as pure piroxicam.
J.
ˇ
Sebest
´
ık et al., Biomedical Applications of Peptide-, Glyco- and Glycopeptide
Dendrimers, and Analogous Dendrimeric Structures,
DOI 10.1007/978-3-7091-1206-9
105
10, © Springer-Verlag Wien 2012
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106 10 Dendrimers and Solubility
Fig. 10.1 Various ways of drug solubilization by dendrimers [21, 26]. The figure was reprinted
from [21] with kind permission of Springer, Wien–NewYork
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