Mesoporous self-assembled nanoparticles of biotransesterified cyclodextrins and nonlamellar lipids as carriers of water-insoluble substances.

Soft mesoporous hierarchically structured particles were created by the self-assembly of an amphiphilic deep cavitand cyclodextrin ßCD-nC10 (degree of substitution n = 7.3), with a nanocavity grafted by multiple alkyl (C10) chains on the secondary face of the ßCD macrocycle through enzymatic biotransesterification, and the nonlamellar lipid monoolein (MO). The effect of the non-ionic dispersing agent polysorbate 80 (P80) on the liquid crystalline organization of the nanocarriers and their stability was studied in the context of vesicle-to-cubosome transition. The coexistence of small vesicular and nanosponge membrane objects with bigger nanoparticles with inner multicompartment cubic lattice structures was established as a typical feature of the employed dispersion process. The cryogenic transmission electron microscopy (cryo-TEM) images and small-angle X-ray scattering (SAXS) structural analyses revealed the dependence of the internal organization of the self-assembled nanoparticles on the presence of embedded ßCD-nC10 deep cavitands in the lipid bilayers. The obtained results indicated that the incorporated amphiphilic ßCD-nC10 building blocks stabilize the cubic lattice packing in the lipid membrane particles, which displayed structural features beyond the traditional CD nanosponges. UV-Vis spectroscopy was employed to characterize the nanoencapsulation of a model hydrophobic dimethylphenylazo-naphthol guest compound (Oil red) in the created nanocarriers. In perspective, these dual porosity carriers should be suitable for co-encapsulation and sustained delivery of peptide, protein or siRNA biopharmaceuticals together with small molecular weight drug compounds or imaging agents.

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

A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, ß-, 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.