Each drug deserves a cyclodextrin soul mate: Design and tailoring of suitable derivatives for the encapsulation and revitalization of existing drugs

Cyclodextrins (CDs) are hydrophilic, biocompatible macrocyclic oligosaccharides enzymatically obtained from starch. The most popular α-, β- and γCDs consist, respectively, of 6, 7 and 8 α-D-glucopyranose units joined together by α(1-4) linkages (Figure 1A). While being soluble in water thanks to the hydrophilic exterior, their cavity is endowed with a hydrophobic character enabling supramolecular interactions with a wide variety of substrates. The formed host:guest complexes could be exploited in many applications, from food and cosmetic industry to environmental technologies. However, the full potential of CDs has been capitalized in the pharmaceutical field, due to the ability of CD-based, non-toxic, smart carriers to enhance the stability, bioavailability and water solubility of hydrophobic drugs. Besides, CDs are emerging as intrinsic therapeutics. This presentation will uncover the synthesis of mono-, poly- and fully substituted CDs bearing finely tuned functional groups designed to enhance their binding properties towards specific targets (Figure 1B). Regio-selective modification, achieved exploiting the different reactivity of the hydroxy groups in positions 2, 3 and 6 of the glucose units, resulted in cationic1 and anionic2 CD-derivatives used to combat antimicrobial resistance mechanisms. These optimized molecules stabilized negatively charged penicillin antibiotics and were able to significantly bind metal cations, respectively. Further, the preparation and use of βCD-polymers crosslinked with epichlorohydrin will be introduced.3 These neutral materials are able to co-encapsulate simultaneously more than one guest and were used as inert support for the photocatalytic conversion of aromatic substrates into their corresponding endoperoxides. Such supramolecular complex was then tested as delivery system for the guests capable to selectively release the trapped molecular oxygen once reached the target tumour tissues.4