CyDs chemically modified

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,... 

In 2003, the first chemically modified LR-CyD (CyD9) was synthesized to enhance chemiluminescence efficiency by forming a CyD-bound luciferin analogue, but CyDg did not show a high chemiluminescence efficiency in comparison with regular CyDs (especially, y-CyD) [32],... 

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... 

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