Cyclodextrins for Pharmaceutical and Biomedical Applications

Abstract

Cyclodextrins have occupied a preferential position in supramolecular chemistry and pharmaceutical technology for decades. Their molecular structure provides them with unique supramolecular features that have already found a plethora of applications for numerous purposes, including innovative solutions to formerly unmet pharmaceutical and biomedical challenges. The amalgamation of chemical, supramolecular and technological knowledge and the paradigmatic correlation between cyclodextrin structure and function has facilitated an unprecedent and fluent crosstalk among formerly distant research disciplines. This chapter emphasizes the role that cyclodextrins are playing in the era of nanosciences and the recent advances in cyclodextrins chemistry and technology that are making it feasible to address a broad range of pharmaceutical and biomedical challenges. A series of examples illustrates how the knowledge gained over a century of cyclodextrin research can applied: (i) for manipulation of the bioavailability of therapeutic agents, (ii) for the rational design of intelligent systems envisioned for targeted delivery and programmed release of cargos, (iii) for devising new therapeutic strategies for known maladies, and (iv) for the engineering of biosensing devices.

Cyclodextrin-Based Functional Glyconanomaterials

“…The efficiency in compacting nucleic acids into nanocomplexes (so-called CDplexes) capable of mediating cell entry and subsequent expression of the nucleic acid anticipated activity (transfection) was significantly enhanced for prototypes that can additionally establish cyclodextrin-cyclodextrin interactions through either hydrophobic , host-guest [79,134] or aromatic-aromatic contacts [135][136][137][138][139][140][141][142][143][144][145][146]. As a logical extension, the formulation of CDplexes exposing biorecognizable ligands for the purpose of site-specific gene delivery has been proposed [147][148][149][150][151][152][153][154][155], including the elaboration of carbohydrate decorated CDplexes (glycoCDplexes) conceived for cell receptor glycotargeting [3]. In a first attempt, García Fernández and coworkers prepared three-component supramolecular assemblies from a multi-head/multi-tail polycationic amphiphilic CD displaying 14 primary amino groups (paCD-N 14 ), a glycoamphiphilic CD (GaCD) bearing mannosyl residues at the seven primary βCD positions (GaCD-Man 7 ) and a luciferase-encoding plasmid DNA (pDNA; pTG11236, 5739 bp) ( Figure 13) [156].…”

“… Docetaxel (DTX) carrier consisting of a hexamannosylated dimeric βCD derivative designed on the basis of the drug clusterization concept [ 35 ]. Adapted with permission from Reference [ 3 ]. Copyright 2013 Royal Society of Chemistry.…”

“…The stability and water solubility of the guest can be improved in this manner, or the target guest can be captured, removed or masked, broadening application scopes. Indeed, the academic and (bio)technological interest for cyclodextrins has been historically dominated by their inclusion complex-formation ability, which has translated into numerous applications in fields like food [ 1 , 2 ], cosmetics [ 3 ], environment [ 4 , 5 ], and medicine [ 3 , 6 , 7 , 8 , 9 , 10 ].…”

Cyclodextrin nanoassemblies: a promising tool for drug delivery

“…In fact, they are used extensively in pharmaceutical formulations to encapsulate drugs to protect them or to enhance solubility [13]. CDs are cyclic oligosaccharides composed of 6 (a-), 7 (b-) or 8 (g-) glucose units linked by a-1,4 glycosidic bonds.…”

Simple degradable cyclodextrin polyester with chelator-based crosslinker for stent-based drug delivery

“…CDs, with their hydrophobic cavities, are particularly adept at forming inclusion complexes with small hydrophobic molecules; in other words, CDs have affinity for many small hydrophobic drugs. CDs have historically been used in pharmacological applications to solubilize and improve bioavailability of drugs in vivo as well as to draw organic compounds out of solution, 2,3 and more recently as polymerized nanosponges, hydrogels, and particles for drug delivery. 4,5 Polymerizing CD into highly crosslinked networks increase the likelihood of drug interactions with CD pockets, leading to increased drug loading and more linear drug release profiles compared to polymers without similar affinity.…”