Hydrophilic cyclodextrins

The highly evolved catalyst 20 combines several features that have proved successful in simpler cases. The ionic sulfonate groups make the substrate sufficiently soluble for the reaction to be run in water. (The four hydrophilic cyclodextrins perform the same service for the catalyst.) The target reaction, the seledive oxidation of the steroid skeleton, goes back to the early days of enzyme models,1711 and the choice of porphyrin and of manganese as the metal cation are based on many years experience. The aryl groups are perfluorinated because an earlier version of the catalyst suffered self-oxidation. 

Rode, T., Frauen, M., Muller, B. W., Dusing, FI. J., Schonrock, U., Mundt, C., andV fenck, FI. 2003. Complex formation ofsericoside with hydrophilic cyclodextrins improvement of solubility and skin penetration in topical emulsion based formulatiorfsur. J. Pharm. Biopharm. 55 191-198. 

Pitha, J., S. Harma, and M. Michel. 1986. Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones. J Pharm Sci 75 165. 

Badawy, S.I.F. Ghorab, M.M. Adeyeye, C. Study of the complexation between danazol and hydrophilic cyclodextrin derivatives. Pharm. Res. 1995,12 (9), S204. 

Another aqueous heterogeneous polymerization was recently reported for the precipitation polymerization of MMA and styrene complexed with methylated /3-cyclodextrin.256 The polymerization was carried out in water with 1-21 (X = Br)/CuBr/L-4 to give polymers with controlled molecular weights and relatively narrow MWDs (MJMn = 1.3—1.8). Initially, the reaction mixture was homogeneous with the hydrophilic cyclodextrin-complexed MMA, but sooner or later it became heterogeneous due to the formation of water-insoluble polymers. 

Itraconazole, a widely used broad-spectrum anti-fungal agent has been used as an example (De Beule and Van Gestel, 2001 Peeters et al., 2002). As indicated in Figure 3, the compound is predicted to have extremely low water solubility but useful intestinal permeability. The parameter sensitivity analysis indicated that fraction absorbed could be substantially increased if the apparent solubility of the drug could be increased to 100 pg/mL or greater. Such manipulation is possible through the use of hydrophilic cyclodextrins such as 2-hydroxypropyl-... 

Cyclodextrins have been used for enhancing the solubility of poorly water-soluble small molecules (Shimpi et ah, 2005). The mechanism of solubilization is formation of reversible complexes between the hydrophobic moiety of the drug molecule and the hydrophilic cyclodextrin that is highly water soluble. A similar observation has been made with some proteins and peptides (Brewster et ah, 1991 Johnson et ah, 1994 Flores et ah, 2001). Sulfated cyclodextrins and 2-hydroxypropyl-beta-cyclodextrins are approved excipients for parenteral administration, however, use of these compounds should take into consideration the cost involved. 

Also, liposomes (see later) are very similar but are formed by the self-assembly of phospholipid molecules in an aqueous environment. The amphiphilic phospholipid molecules form a closed spherical bilayer in an attempt to shield their hydrophobic groups from the aqueous environment, whilst still maintaining contact with the aqueous phase via the hydrophilic head group. The resulting closed sphere may encapsulate water-soluble drugs within the inner aqueous compartment or may encapsulate lipid soluble drugs within the bilayer membrane. Alternatively, lipid soluble drugs may be complexed with a hydrophilic cyclodextrin and then encapsulated within the liposome aqueous compartment. 

A number of examples of the use of host-guest chemistry in the creation of PET active systems have appeared. The reaction of P-cyclodextrin alcoholate with meso-tetrakis(pentafluorophenyl)porphyrin is reported to give a hydrophilic cyclodextrin-porphyrin conjugate in 14% yield. ° In the presence of guests such as 1,4-benzoquinone, anthraquinone-2-sufonate or 8-anilino-l-naphthalene sulfonic acid, PET operates as evidenced by the fluorescence... 

Tavornvipas S, Tajiri S, Hirayama F, et al. (2004). Effects of hydrophilic cyclodextrins on aggregation of recombinant human growth hormone. Pharm. Res. 21 2369-2376. 

Cyclodextrin-based drug delivery systems The hydrophilic cyclodextrins have been extensively )plied to enhance the oral bioavailabilily of steroids, cardiac glycosides, nonsteroidal anti-inflammatory drugs, barbiturates, antiepileptics, benzodiazepines, antidiabetics, vasodilators, etc. Delayed and prolonged release of diltiazem and molsidormine was achieved by their complexation with CD derivatives, modified release of nifedipine can be achieved by its complexation with 2-HP-P-CD fiirosemide and piretanide (loop diuretics) release can be modified after complexation with DM-P-CD. Prednisolone dosage forms can be optimized also by complex-formation with 2-HP-P-CD. 

On a laboratory scale, the complexes are prepared by the coprecipitation method the guest is added to an aqueous solution of the hydrophilic cyclodextrin. The complex is usually less soluble, precipitates and can be isolated by filtration or centrifugation. For water-insoluble guests, diethyl ether can be used to facilitate the phase transfer. The ether then can be blown away by bubbling argon through the solution. The main driving forces for the complex formation are hydrophobic and van-der-Waals interactions. These are the... 

Cyclodextrins are macrocyclic compounds comprised of D-glucose bonded through 1,4-a-linkages and produced enzymatically from starch. The greek letter which proceeds the name indicates the number of glucose units incorporated in the CD (eg, a = 6, /5 = 7, 7 = 8, etc). Cyclodextrins are toroidal shaped molecules with a relatively hydrophobic internal cavity (Fig. 6). The exterior is relatively hydrophilic because of the presence of the primary and secondary hydroxyls. The primary C-6 hydroxyls are free to rotate and can partially block the CD cavity from one end. The mouth of the opposite end of the CD cavity is encircled by the C-2 and C-3 secondary hydroxyls. The restricted conformational freedom and orientation of these secondary hydroxyls is thought to be responsible for the chiral recognition inherent in these molecules (77). 

Addition of a chiral carrier can improve the enantioselective transport through the membrane by preferentially forming a complex with one enantiomer. Typically, chiral selectors such as cyclodextrins (e.g. (4)) and crown ethers (e.g. (5) [21]) are applied. Due to the apolar character of the inner surface and the hydrophilic external surface of cyclodextrins, these molecules are able to transport apolar compounds through an aqueous phase to an organic phase, whereas the opposite mechanism is valid for crown ethers. 

Complex Formation of Cyclodextrins with Hydrophilic Polymers. 144... 

Table 1. Comparison of hydrophilic polymers with various chain cross-sectional areas in formation of crystalline complexes with cyclodextrins...

Recently, we have also prepared nanosized polymersomes through self-assembly of star-shaped PEG-b-PLLA block copolymers (eight-arm PEG-b-PLLA) using a film hydration technique [233]. The polymersomes can encapsulate FITC-labeled Dex, as model of a water-soluble macromolecular (bug, into the hydrophilic interior space. The eight-arm PEG-b-PLLA polymersomes showed relatively high stability compared to that of polymersomes of linear PEG-b-PLLA copolymers with the equal volume fraction. Furthermore, we have developed a novel type of polymersome of amphiphilic polyrotaxane (PRX) composed of PLLA-b-PEG-b-PLLA triblock copolymer and a-cyclodextrin (a-CD) [234]. These polymersomes possess unique structures the surface is covered by PRX structures with multiple a-CDs threaded onto the PEG chain. Since the a-CDs are not covalently bound to the PEG chain, they can slide and rotate along the PEG chain, which forms the outer shell of the polymersomes [235,236]. Thus, the polymersomes could be a novel functional biomedical nanomaterial having a dynamic surface. 

The ORAC assay proposed by Ou and others (2001) is limited to hydrophilic antioxidants because of the aqueous environment of the assay. However, lipophilic antioxidants play a critical role in biological defense systems. Huang and others (2002) expanded the assay to the lipidic fraction by introducing a randomly methylated 13-cyclodextrin (RMCD) as a water-solubility enhancer for lipophilic antioxidants. Various kinds of foods, including fruit juices and drinks, fruits, vegetables, nuts, and dried fruits, have been evaluated with this method (Zhou and Yu 2006 Wu and others 2004 Kevers and others 2007 Wang and Ballington 2007 Almeida and others 2008 Mullen and others 2007). 

In principle, there are four basic strategies to compensate for the repulsive effects between the hydrophobic fullerene surface and water (a) encapsulation in the internal hydrophobic moiety of water-soluble hosts like cyclodextrins (Andersson et al., 1992 Murthy and Geckeler, 2001), calixarenes (Kunsagi-Mate et al., 2004) or cyclotriveratrylenes (Rio and Nierengarten, 2002) (b) supramolecular or covalent incorporation of fullerenes or derivatives into water-soluble polymers (Giacalone and Martin, 2006) or biomolecules like proteins (Pellarini et al., 2001 Yang et al., 2007) (c) suspension with the aid of appropriate surfactants and (d) direct exohe-dral functionalization in order to introduce hydrophilic moieties. 

Multihydroxyl containing monomeric or oligomeric p-cyclodextrins (PCD) such as those attained by grafting with glycidyl ethers of protected polyols (glycerol and pentitols) appeared rather promising components for their amphiphilic character, connected to the presence of an hydrophobic pocket and an external hydrophilic shell with an amplified number of hydroxyl groups. 

Spherical pellets containing 5% triamcinolone acetonide were prepared by Villar-Lopez and co-workers [59] by extrusion/spheronization following formulation with microcrystalline cellulose and/or a hydrophilic excipient like lactose, sodium earbox-ymethylcellulose, or P-cyclodextrin. Their suitability for coating, with a view toward colonic drug deliveiy, was assessed in terms of their size, sphericity, and dissolution test response. The best results were afforded by a 5 90 5 composition of microcrystalline cellulose, P-cyclodextrin, and triamcinolone acetonide, prepared by complex-ation of triamcinolone acetonide with P-cyclodextrin prior to the addition of microcrystalline cellulose. 

We begin with an excerpt from Environmental Science Technology (excerpt 4B). In a combined R D section, the authors tell us what happened when they coated different types of soil with randomly methylated P-cyclodextrins (RAMEB). Cyclodextrins are highly water-soluble, crystalline sugars their shape (referred to as toroidal) resembles a water pail without a bottom. The outer surfaces of the pail are hydrophilic (water-loving), which accounts for their solubility in water and their ability to attract water molecules. RAMEB alone adsorbs water molecules hence, the authors predicted that RAMEB-coated soils would adsorb more water than their noncoated counterparts. 

We describe how we prepared and characterized gold nanoparticles ( 3 nm in diameter) capped with thiolated cyclodextrins. The CD-capped nanoparticles are hydrophilic, and they bind compounds derivitized from ferrocene as evidenced by values measured by NMR spectroscopy. (Adapted from Liu et al., 2001)... 

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