Cyclodextrin-Based Polymeric Materials: Synthesis, Properties, and Pharmaceutical/Biomedical Applications

Abstract

This review describes the synthesis, properties, and, in particular, biomedical and pharmaceutical applications of an upcoming class of polymeric networks and assemblies based on cyclodextrins (CDs). CDs are cyclic oligosaccharides composed of alpha-1,4-coupled d-glucose units, which contain a hydrophobic internal cavity that can act as a host for various, generally lipophilic, guest molecules. Because of this unique physicochemical property, commonly referred to as inclusion complex formation, CDs have often been used to design polymeric materials, such as hydrogels and nanoparticles. Polymeric systems based on CDs exhibit unique characteristics in terms of mechanical properties, stimuli-responsiveness, and drug release characteristics. In this contribution, first, an outline is given of covalently cross-linked polymeric networks in which CD moieties were structurally incorporated to modulate the network strength as well as the complexation and release of low molecular weight drugs. Second, physically assembled polymeric systems are discussed, of which the formation is accomplished by inclusion complexes between polymer-conjugated CDs and various guest molecule-derivatized polymers. Due to their physical nature, these polymeric systems are sensitive to external stimuli, such as temperature changes, shear forces and the presence of competing CD-binding molecules, which can be exploited to use these systems as injectable, in situ gelling devices. In recent years, many interesting CD-containing polymeric systems have been described in literature. These systems have to be optimized and extensively evaluated in preclinical studies concerning their safety and efficacy, making future clinical applications of these materials in the biomedical and pharmaceutical field feasible.

Preorganized, Macromolecular, Gene‐Delivery Systems

“…However, CDs can also be viewed as nanometric platforms with two well-differentiated faces: the narrower rim bearing the primary OH-6 hydroxyl groups and the wider rim, in which the secondary OH-2 and OH-3 hydroxyl groups are located (Figure 8). By using either specific-position or facial-selective functionalization methodologies, it is possible to incorporate cyclodextrin moieties in macroA C H T U N G T R E N N U N G mol-A C H T U N G T R E N N U N G ecular constructs, for example, polymers [50] and dendri-A C H T U N G T R E N N U N G mers, [51] to install a variety of functional elements with a precise spatial orientation and density onto a CD scaffold, [52] or Figure 7. Structure of amphiphilic aminocalixarenes with different valencies.…”

Cholesterol Depletion Using Methyl-β-cyclodextrin

“…Cyclodextrins are water-soluble oligosaccharides containing hydrophobic cavities [14,15]. Cyclodextrins contain a-(1-4) linked D-glycopyranose units which can form hexamers (α-CD), heptamers (β-CD) (Fig.…”

“…The number of glycopyranose units in the ring structure and the degree of polymerization determines the size of the hydrophobic cavity and the affinity towards specific compounds. The water solubility of cyclodextrins can be improved by various modifications including methylation [14,15]. Based on the dimensions of their cavities, α-CD can form inclusion complexes only with low-molecular-weight molecules or compounds with aliphatic side chains, β-CD can form complexes aromatic or heterocyclic compounds, while γ-CD can accommodate a wider variety of large organic compounds such as macrocycles and steroids [16].…”

Construction and Degradation of Polyrotaxane Multilayers

“…The polyvalent character of polyelectrolyte PRXs will disappear upon α CD dethreading, resulting in degradation of the fi lm, which is initiated by cleavage of the disulfi de bonds linking the capping groups ( Figure 1 ). The degradation products, linear PEG chains, [ 3 ] and the relatively small α CDs [ 2 ] have been reported to be biocompatible. Unlike multilayers made from CDs conjugated to polyelectrolytes for the complexation and retention of drugs in the layers, [ 24 ] our system provides the possibility for drug incorporation via conjugation to threaded α CDs, [ 9 ] which Scheme 1 .…”