Hydrogels with cyclodextrins as highly versatile drug delivery systems

Cyclodextrins (CDs) are cyclic oligosaccharides that combine a hydrophobic cavity with a hydrophilic surface. This unique characteristic confers the CDs the ability to form inclusion complexes with a wide range of drugs. Their complexation ability has been widely exploited as a mean to increase the solubility and stability of drugs in liquid formulations or to promote drug dissolution from solid formulations. CD-functionalized materials may open new perspectives in phamacotherapy. Combination of the features of CDs and hydrogels in a single hybrid material is particularly attractive. Hydrogels have emerged as very suitable platforms for developing advanced drug delivery systems (DDS) owing to their renowned biocompatibility, fine tunable mechanical properties and versatile composition, which makes them suitable for any delivery route. Nevertheless, their performance as DDS is somehow limited when a high loading of hydrophobic drugs (that dislike the aqueous phase of the hydrogels) or when a precise control of the delivery of hydrophilic drugs is required. CDs can overcome these limitations providing the hydrogels with complexation functionality. The CD cavities can act as suitable reservoirs for hosting poorly-water soluble drugs within the aqueous environment of the network, leading to a remarkable increase in the network/water partition coefficient of the drug. Furthermore, the cross-linked structure leads to a microenvironment rich in CDs that do not disassembly under dilution in the biological fluids. Such highly rich CD domains prevent from a fast drug decomplexation, resulting in a controlled delivery even for hydrophilic drugs. This chapter analyzes the role of movable CDs in semisolid or solid networks and of fixed CDs in cross-linked networks, and revise the main approaches developed for preparing CD-based hydrogels: i) direct cross-linking of CDs through condensation reactions with di- or multifunctional reagents, ii) free radical copolymerization of CD derivatives with acrylic monomers, and iii) grafting of CDs to preformed hydrogels. Examples of the performance of CD hydrogels as DDS, including stimuli-responsive systems, are presented and their practical applicability discussed.