Cyclodextrin Bilayer Vesicles

Abstract

Over the past decade, several groups have reported amphiphilic cyclodextrin derivatives that display a range of lyotropic and thermotropic mesophases. Amphiphilic cyclodextrins have been shown to form monolayers at the air ± water interface [1] and micelles in water. [2] Thermotropic liquid crystals of cyclodextrins were also described. [3] Amphiphilic cyclodextrins can be admixed in limited percentages to phospholipid monolayers [4] as well as liposomes, [5] and they can be dispersed as ªnanoparticlesº of pharmaceutical interest. [6] However, with few exceptions, these materials have poor water solubility. We have now prepared the first examples of bilayer vesicles composed entirely of amphiphilic cyclodextrins. These vesicles combine the properties of liposomes and macrocyclic host molecules, and create new possibilities for the development of advanced host ± guest carrier and delivery systems. Some examples of vesicles composed of amphiphilic macrocycles such as calixarenes [7] and cryptands [8] were recently described.Heptakis(6-alkylthio)-b-cyclodextrins [3] display thermotropic mesophases and form monolayers at the air ± water interface, [1f,g, 3, 9] but are practically insoluble in water. The poor water solubility of these cyclodextrins most likely results from intramolecular hydrogen bonding of the secondary hydroxyl groups, as is the case for unmodified b-cyclodextrin. Attempts to ªbreakº this hydrogen-bond network by persubstitution of the secondary side by methyl and acetyl groups only slightly improved the water solubility. [9] However, we demonstrate herein that substitution of the secondary side with hydrophilic hydroxyethyl groups dramatically improves the water solubility (as observed previously for random and low-degree substitution of b-cyclodextrin [10] ), and provides cyclodextrins with pronounced amphiphilic character.Cyclodextrins 4 and 5 were obtained in a three-step synthesis from b-cyclodextrin. b-Cyclodextrin was per-brominated at the C 6 positions, [11] and the resulting heptakis(6bromo-6-deoxy)-b-cyclodextrin (1) yielded the 6-alkylthioethers 2 and 3 by reaction with potassium n-dodecylthiolate and n-hexadecylthiolate, respectively. [3] Subsequently, we developed an efficient modification of the hydroxyethylation process for b-cyclodextrin, [10] which uses ethylene carbonate as the alkylating agent. We found that 2 and 3 can be efficiently hydroxyethylated in tetra-N-methylurea (TMU) at 150 8C using an excess of ethylene carbonate and adding 10 % of K 2 CO 3 as base. [12] The elevated temperature is essential for rapid and extensive substitution. Cyclodextrin 4 was purified

Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis, Formulation and Characterization

“…The height difference between 14 and 15 was ascribed to the fact that the structure based on shorter alkyl chain ( 14 ) may have been slightly more rigid, with less flattening of the structures. In all the cases the observed heights are much greater than those observed for other vesicular nanostructures based on cyclodextrins [ 87 ] and calix-resocinarenes [ 88 ]. This observation confirms the solid structure of this kind of colloidal particles.…”

Molecular Recognition of Polymers by Cyclodextrin Vesicles

“…Multiple, instead of isolated, host-guest interactions enhance binding affinity as well as selectivity. [1] Here we have investigated the role of multiple noncovalent interactions in molecular recognition at a membrane surface by using a model system consisting of bilayer vesicles of hydrophobically modified cyclodextrins [2] (CDs; the membrane receptors) in combination with monomer and polymer guest molecules [3] (the substrates). Molecular recognition and multiple host-guest interactions have been described for CD dimers [4] (including CD dimers in the presence of liposomes [5] ) and polymers [3,6] as well as CD micelles [7] and self-assembled CD monolayers.…”

“…[10] The formation of bilayer vesicles from this CD was described previously. [2] Cyclodextrin vesicles consist of bilayers of cyclodextrins (in which the hydrophobic "tails" are directed inwards and hydrophilic macrocycle "head groups" are facing water) enclosing an aqueous interior. In this work, we used unilamellar vesicles prepared from multilamellar vesicles by repeated extrusion through a polycarbonate membrane (pore size 0.1 mm) which according to dynamic light scattering (DLS) studies have an average hydrodynamic diameter of approximately 160 nm.…”

Cyclodextrin-Based Functional Glyconanomaterials

“…The vesicular nanoplatform was obtained from CD precursors where all primary hydroxyls have been replaced by dodecylthio tails and some of the secondary hydroxyls, mainly O-2-positions, are etherified with ethylene carbonate. The latter reaction results in the installation of oligo(ethylenglycol) chains, which on average are diethylenglycol residues, thereby creating a hydrophilic domain [ 180 ]. In spite of bearing a certain polydispersity, the self-assembled CDVs (average hydrodynamic diameter ≈ 120–150 nm) engineered from these CDs are very stable and behave as host membranes [ 181 ].…”