Dendrimers and Solubility
Solubility is a key property influencing behavior of compounds in nature, science, biomedical applications, etc. Hydrophobicity and poor solubility of drugs and other bioactive compounds limit their possible applications in drug delivery and formulation d
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Dendrimers and Solubility
Hydrophobicity of drugs and bioactive compounds reduces their solubility in water and significantly diminishes their activity in vivo [21]. Only 60 % of drug candidates reach the patients, whereas the remaining 40 % of compounds are 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, hydrogen 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 encapsulation (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 applied as solubilizers of various drugs [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. ˇ J. Sebest´ ık et al., Biomedical Applications of Peptide-, Glyco- and Glycopeptide Dendrimers, and Analogous Dendrimeric Structures, DOI 10.1007/978-3-7091-1206-9 10, © Springer-Verlag Wien 2012
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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
10 Dendrimers and Solubility
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Another example is 1,000-fold solubility enhancement of the anticancer drug docetaxel [5] by the inclusion complexes of ˇ-CD dendrimers with hexavalent mannosyl ligands. The solubilization power of dendrimers can be improved by PEGylation [26]. A modification of PAMAM surface with PEG and ˇ-CD enlarged the solubility of fullerene
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