Modified CyDs

Cyd, in contrast, gives rise to a sugar-centered radical. The mechanism proposed by (Catterall et al. 1992) has been modified by Aravindakumar et al. (2003) [reactions (42)—(47)] insofar as route (42) is now favored over (43) followed by (44). 

Jarho, P., Jarvinen, K., Urtti, A., Stella, V. J., and Jarvinen, T. (1996), Modified beta-cyclodextrin (SBE7-beta-CyD) with viscous vehicle improves the ocular delivery and tolerability of pilocarpine prodrug in rabbits, J. Pharm. Pharmacol., 48(3), 263-269. 

Recent advances in carbene chemistry demonstrate that constrictive hosts, like CyDs and FAUs zeolites are able to modify the selectivity of the high-energy reaction intermediate.42... 

Instead, the spectra clearly show appreciable amounts of PhCHO CyD (not PhCHO CyD) and only traces of HCl CyD (or CyD HC1) byproducts. The covalently bound character of each modified PhCHO CyD was confirmed by control experiments and RP HPLC. 

Intemasal delivery of peptide and protein drugs is severely restricted by pre-systemic elimination due to enz5miatic degradation or mucociliary clearance and by the limited extent of mucosal membrane permeability. a-CyD has been shown to remove some fatty acids from nasal mucosa and to enhance the nasal absorption of leuprolide acetate in rats and dogs. The utility of chemically modified CyDs as absorption enhancers for peptide drugs in rats has been demonstrated. For example, DM-P-CyD was shown to be a potent enhancer of insulin absorption in rats, and a minimal effective concentration of DM-(3-CyD for absorption enhancement exerted only a mild effect on the in vitro ciliary movement.The scope of interaction of insulin with CyDs is limited, because CyDs can only partially include the hydrophobic amino acid residues in peptides with small stability constants. Under in vivo conditions, these complexes will readily dissociate into separate components, and hence the displacement by membrane lipids may further destabilize the complexes. The direct interaction of peptides with CyDs is therefore of minor importance in the enhancement of nasal absorption. Of the hydrophilic CyDs tested, DM- 3-CyD had the most prominent inhibitory effect on the enzymatic degradation of both BLA and insulin in rat nasal tissue homogenates. Because of the limited interaction between peptides and CyDs,... 

The haemolytic activities of natural CyDs are reported to be in the order p- > a- > y-CyD. These differences are ascribed to the differential solubilization of membrane components by each CyD. When the CyD cavity is modified by chemical derivatization, its effects on cell membranes can be changed dramatically from those of parent CyDS. When the muscle tissue damage due to the injection of hydrophilic CyDs was compared with that of mannitol and nonionic surfactants, following a single injection (100 mg ml" ) of the compounds into M. vastus lateralis of rabbits (Fig. 38.2), a-CyD and DM-P-CyD showed a relatively high irritation reaction, the degree of... 

CyD, HCO-60 and HPCs can serve as a modified-release carrier of nifedipine and can be applied to other poorly water-soluble drugs with short elimination half-lives. 

The first part of this chapter describes methods for modifying CyDs in which the number and exact positions of substituents have been ascertained and where pure compounds with unambiguous structures have been obtained. 

Tosyl j8-CyDs are important precursors for a variety of modified CyDs because a nucleophile can attack the electrophilic carbon at the 6-position to produce a corresponding functionality. The reaction of jS-CyD with tosyl chloride in aqueous alkaline medium gives mono-6-tosylated jS-CyD in fairly good yield [15]. 

A-dansyl-6X-tosyl-modified (X = B or G, C or F, and D or E, see Scheme 2.4) fi-CyDs and y-CyDs were synthesized to investigate their chemo-sensor potential [68]. 

A )8-CyD derivative modified with p-xylylenediamine at the 3-position, mono-3-[4-(aminomethyl)benzylamino]-yS-CyD, was prepared by the reaction of ) -CyD-2,3-manno-epoxide with p-xylylenediamine [97]. The three isomeric mono-2-, 3-, or 6-hydroxy permethylated yS-CyDs are good precursors for a wide variety of monofunctionalized permethyl yS-CyDs. As protecting groups, the benzyloxy group was used for C2, and the t-butyldimethylsilyl group for C6. Mono-C3 hydroxy CyD was obtained by partial methylation of 2,6-dimethyl CyD [98]. 

Various modified CyDs have been prepared to improve their binding affinities and selectivities controlled by external factors such as photons, metal ions, or pH. Such CyDs can act as chemosensors, artificial enzymes, drug carriers, or reaction fields. CyDs have been used as scaffolds for highly preorganizing functional units. There are aheady many reviews on modified CyDs [1-6, 8, 9, 123-125], so here we summarize only developments reported in the last seven years. 

Carboxylate-modified or ammonium-modified CyDs show pH-dependent inclusion phenomena. Therefore it is expected that these charged hosts can be used as pH-triggered guest release systems [157]. For example, 1-pyrenesulfonate was included in the cavity of heptakis(2,3-di-0-carboxymethyl)-jff-CyD 39 with a binding constant of 2300 at pD = 2.0, while no complexation occurred at pD > 6.0. 

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