CyDs amphiphilic

Amphiphilic heptakis(6-alkylthio)- 8-CyD derivatives were synthesized and their monolayer behavior on a water surface was studied on the basis of surface-molecular area [n-K) isotherms [61]. j8-CyD functionalized at the 6-position with trifluoromethylthio groups have been obtained from the native j8-CyD [62]. Heptakis(2,3-dihexanoyl)-yS-CyD, heptakis(6-hexanamido)-j8-CyD, and heptalds(6-myristamido)-j8-CyD have been synthesized and nanocapsules prepared by nanoprecipitation [63]. Heptakis(6-0-amphiphilic)-jS-CyDs with substituents of varying chain lengths (C and C14) and bond types (ester or amide) have been studied [64]. 

Per-amino-CyDs form various self-assemblies by hydrogen bonding in water [159-161]. Cationic amphiphilic j8-CyDs 41, 42, substituted with hydrophobic n-alkylthio chains at the primary hydroxyl side and hydrophilic co-amino-oligo-(ethylene glycol) units at the secondary side, formed bilayer vesicles with a diameter of 30-35 nm (when alkyl = hexadecyl) or nanoparticles with a diameter of ca. 120 nm (when alkyl = hexyl) in water [159]. Sulfated amphiphilic CyDs 43-45... 

Various amphiphilic a- and jS-CyDs functionalized with alkyl chains at the primary hydroxy positions or modified on the secondary face form stable and well-organized monomolecular layers at the air-water interface [47, 48]. They can then be used for the preparation of L-B films on solid substrates. Electroactive CyDs persubstituted with electroactive groups, e.g. terathiafulvalene (TTF) moieties [49], were transferred as L-B films from the water surface with a transfer ratio of 1 to the solid substrate (Fig. 10.5.3). Charge-transfer interactions in the... 

SUV + amphiphilic CyD (sonication or injection) into amphiphilic CyD solution N-alkyl-/ -CyD... 

DPPC/CH SUV + amphiphilic CyD Spray-drying 2,3-di-O alkyl-/ -CyD sulfated... 

Amphiphilic CyDs (Lollipop, Cup-and-ball, Medusa-like, Skirt-shaped, and Bouquet) have been synthesized by the grafting of various substituents to different faces of native CyDs [65]. (Syntheses of CyD derivatives are presented in Chapter 2). Among them. Medusa-like cyclodextrins and Skirt-shaped cyclodextrins have demonstrated their ability to form nanocapsules or nanospheres. 

The nanoprecipitation method also allows the production of nanocapsules oil (Miglyols or benzyl benzoate with or without the drug) is introduced together with the amphiphilic CyD in the organic phase (ethanol or acetone) [47, 61]. 

In this section, lipidic vesicles are classified as follows liposomes, niosomes, and amphiphilic CyD vesicles (Fig. 15.3). 

Other Amphiphilic Cyclodextrins Other amphiphilic CyDs as well as cholesteryl-CyDs can form lipidic vesicles. These vesicles can be liposomes or vesicles delimited by the bilayer of amphiphilic molecules, sometimes incorrectly named liposomes . 

The preparation methods of these vesicles are various. In some cases, the liposomal suspension is firstly prepared and then amphiphilic CyDs are inserted inside the phospholipid-bilayer, for example by sonication [93]. Another method mixes phospholipid (+/— cholesterol) and amphiphilic CyD solutions, to form hposomes by conventional methods [92, 94]. Lastly, vesicles consisting of bilayers of purely amphiphilic CyDs as raw material can be prepared applying a technique used to prepare hposomes, i.e. hydration of lipidic film followed by sonication [99-101]. 

The introduction of amphiphilic CyDs within vesicles presents the following advantages ... 

Amphiphilic CyD Nanoparticles Only a few studies have evaluated the release kinetics from nanoparticles prepared with amphiphilic CyDs [52, 56, 57, 62]. The parameters involved in in vitro release are the nanosphere loading technique, the drug CyD association constant, and the effect of the substitution side. 

The affinity of parent yS-CyD for drugs plays a major role in drug release from amphiphilic f-CyD nanospheres [56]. Indeed, bifonazole, which has a very high association constant with 8-CyD (Ki i = 11000 M ), is released significantly more slowly than clotrimazole, which has a lower association constant (Kiu = 500 M ). 

Amphiphilic f-CyD substituted on the primary face displayed slower release profiles for bifonazole than amphiphilic CyDs substituted on the secondary face. This difference is observed for Preloaded and Highly Loaded Nanospheres, both techniques using preformed inclusion complexes. This result is explained by the easier formation of strong inclusions when the wider secondary face remains free of substitution [56]. 

A major drawback of j8-CyD for parenteral use is its hemolytic effects due to its interaction with red blood cells, as demonstrated in vitro on erythrocyte suspensions. Studies performed on whole blood and erythrocyte suspension samples show that in all concentrations studied amphiphilic j8-CyD nanospheres are less hemolytic than native j8-CyD, because of their hydrophobic substituents [56]. Besides the hy-drophobicity, the self-assembly of amphiphilic j8-CyDs in the form of nanospheres is also believed to reduce the interaction and direct contact of CyD with red blood cells. 

Antimicrobial activity on Candida albicans ATCC 90028 has been reported for amphiphilic -CyD nanospheres loaded with bifonazole and clotrimazole [56]. When drug-loaded amphiphiUc fi-CyD nanospheres are incubated with C. albicans, a synergistic effect is observed. Indeed, MIC (Minimal Inhibitory Concen-... 

Finally, Skiba et al. report the in vivo application of indomethacin-loaded nanocapsules, prepared from amphiphilic jS-CyD substituted on the secondary face by Ce chains, jS-CyDCe, in a rat model [48]. They compared the rat gastric ulcerative effect of encapsulated indomethacin with that of the indomethacin solution (Indoc-id ). Independently of the administered dose, the ulcerative effect was significantly decreased while the bioavailability of indomethacin was maintained. Gastrointestinal ulcer protection by encapsulation of indomethacin in jS-CyDC nanocapsules was 82% for 5 mg kg and 53% for 10 mg kg administered dose. 

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