Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

Abstract

A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, β-, or γ-cyclodextrins, have been designed towards innovative applications of self-assembled cyclodextrin nanomaterials. Amphiphilic cyclodextrins have been obtained by chemical or enzymatic modifications of their macrocycles using phospholipidyl, peptidolipidyl, cholesteryl, and oligo(ethylene oxide) anchors as well as variable numbers of grafted hydrophobic hydrocarbon or fluorinated chains. These novel compounds may self-assemble in an aqueous medium into different types of supramolecular nanoassemblies (vesicles, micelles, nanorods, nanospheres, and other kinds of nanoparticles and liquid crystalline structures). This review discusses the supramolecular nanoarchitectures, which can be formed by amphiphilic cyclodextrin derivatives in mixtures with other molecules (phospholipids, surfactants, and olygonucleotides). Biomedical applications are foreseen for nanoencapsulation of drug molecules in the hydrophobic interchain volumes and nanocavities of the amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), anticancer phototherapy, gene delivery, as well as for protection of instable active ingredients through inclusion complexation in nanostructured media.

Characterisation of Inclusion Complexes Between Bifonazole and Different Cyclodextrins in Solid and Solution State

“…The concept of amphiphilic CDs is based on modulation of the hydrophobic/hydrophilic balance of their construction and modulation of their selfassembly properties through grafting of single or multiple substituents on the primary, secondary, or both faces of native CDs. Due to these features, CDs are able to form water-soluble inclusion complexes with many poorly soluble lipophilic drugs [9][10][11][12].…”

Aggregation of Cyclodextrins: Fundamental Issues and Applications

“…These include native and modified CDs, inclusion complexes and the respective aggregates and also rotaxanes and polyrotaxanes, nanotubes, and other high-order structures, such as nanospheres and network aggregates [70]. The potential uses of these self-assembled nanomaterials have been explored for advanced applications, ranging from drug solubilization and drug delivery [71], selective binding [72], and controlled adsorption [72].…”

“…The potential uses of these self-assembled nanomaterials have been explored for advanced applications, ranging from drug solubilization and drug delivery [71], selective binding [72], and controlled adsorption [72]. In pharmaceutical and biomedical fields, it is expected that such applications may include (i) the nanoencapsulation of drugs in the hydrophobic interchain volumes and nanocavities of modified CDs, which can be used as drug carriers or pharmaceutical excipients, (ii) anticancer phototherapy, (iii) gene delivery, and (iv) protection of unstable active components through the formation of inclusion complexes [70]. Several interesting examples of these potential applications have been focused on amphiphilic CDs, which allow to easily modulate both hydrophobic/hydrophilic and self-assembly properties, by grafting different substituents on the portals of native CDs [70,73].…”

“…In pharmaceutical and biomedical fields, it is expected that such applications may include (i) the nanoencapsulation of drugs in the hydrophobic interchain volumes and nanocavities of modified CDs, which can be used as drug carriers or pharmaceutical excipients, (ii) anticancer phototherapy, (iii) gene delivery, and (iv) protection of unstable active components through the formation of inclusion complexes [70]. Several interesting examples of these potential applications have been focused on amphiphilic CDs, which allow to easily modulate both hydrophobic/hydrophilic and self-assembly properties, by grafting different substituents on the portals of native CDs [70,73]. For instance, supramolecular assemblies based on CD/porphyrin nanoassemblies have been studied in vitro [74] as potential nanotherapeutics in A375 human melanoma cells.…”

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

“…The types of aggregation in cyclodextrin drug systems have been extensively researched and reviewed by Loftsson and his collaborators (Loftsson andBrewster, 1996, 2012;Loftsson et al, 2002Loftsson et al, , 2004Messner et al, 2010Messner et al, , 2011Jansook et al, 2010;Loftsson, 2014), Supramolecular assemblies of amphiphilic cyclodextrins alone or in self-assembled mixtures with other molecules of therapeutic significance are described in a recent review by Zerkoune et al (2014). A bis-adamantine molecule which binds cyclodextrins at both ends and forms a hydrophilic -cyclodextrin bis-inclusion complex has been shown to selfassemble into supramolecular vesicles (Nayak and Gopidas, 2015).…”