Delivery of pharmaceuticals and other active ingredients with their crystalline cyclodextrin inclusion compounds

In honor of Prof. Thorsteinn Loftsson's 70th birthday, we offer this personal review of our work using cyclodextrins (CDs) complexed with a variety of active ingredients, including pharmaceuticals, for the purpose of improving their delivery to polymer materials, e.g., fibers, films, hydrogels, etc. Using the affinity of CDs to host and form non-covalent inclusion complexes (ICs) with guest molecules, including a variety of high molecular weight polymers, it is possible to readily deliver these guest molecules into polymer materials via either melt or solution processing of their crystalline or soluble guest molecule-CD-ICs or -rotaxanes. This provides the following advantages: i. CDs are non-toxic, implantable, and biodegradable and have earned the GRAS rating from the FDA. ii. Guest molecules, even those that are neat liquids, can form solid crystalline CD-ICs that are thermally stable to ~ 200 °C and above. This approach permits facile melt-processing into polymer materials for delivery without migration, loss, or degradation of the active guest ingredient. iii. For guests harmful and toxic to their users and the environment, delivery in the form of crystalline CD-ICs can limit any contact with and release of the included toxic guests before they function and are used. iv. It has been demonstrated that, by simple precipitation methods, neat as-received CDs that adopt cage crystal structures can be readily transformed to their columnar crystal structures containing only water in their channels, which can be easily displaced by small molecule, as well as polymer guests. v. Guest-CD-rotaxanes are water soluble, they protect the threaded guest from sources of degradation, and the CD hydroxyl groups may be modified to direct the guest-CD-rotaxane to specific substrates. For these reasons, here we summarize our contributions to the study of CD inclusion and delivery of a variety of guest molecules, including antibacterials, spermicides, insecticides, flame retardants, and dyes, that can more usefully functionalize polymer materials.