Syringeable Self-Assembled Cyclodextrin Gels for Drug Delivery

Abstract

The design of syringeable cyclodextrin (CD) gels is a developing area in the drug delivery and tissue engineering fields, since they offer the possibility of being administered with minimally invasive maneuvers to form depots that can remain for prolonged time in the implantation site. Two different supramolecular systems can be obtained exploiting the capability of CDs to form inclusion complexes. (i) The threading of free CDs on certain blocks or side chains of copolymers leads to polypseudorotaxanes, which can assembly via regular stacking of the threaded CDs. The resultant assemblies can be reversible broken under a certain shear stress and reformed at rest, exhibiting thixotropy that enables the flow through the syringe and the gel recovery in the implantation site. (ii) CDs grafted to polymer chains can develop their ability to form inclusion complexes with complementary guest moieties in other polymeric structures. The result is a ladder- or zipper-like arrangement, which can be also broken and reformed under certain stress conditions. Both types of CDsupramolecular gels can load and stabilize a variety of drugs via interaction with available polymer functional groups or with the CDs that are not participating in other complexes. Moreover, since the complex formation depends on various external and internal variables of the body, the syringeable CD gels can also provide stimuli-responsive drug release. This review focuses on the two main types of syringeable CD gels, prepared via self-aggregation of poly(pseudo)rotaxanes and via zipper-like assembly of CD-functionalized and guest-functionalized macromolecules, and analyzes the mechanisms and variables involved in the gelling processes and the most recent applications in the drug delivery field.