Exploring Cyclodextrin-Based MOFs for Drug Delivery: Synthesis, Applications, and Future Perspectives

Three-dimensional (3D) metal-organic frameworks (MOFs), are known by various names, such as organic zeolite analogues, 3D porous coordination polymers, hybrid organic-inorganic materials, coordination polymers, and metal-organic polymers, are advanced three-dimensional materials distinguished by their high surface area, tunable surface properties, and well-defined crystalline structures. Due to these exceptional characteristics, MOFs have been extensively explored for applications in diverse fields, including gas storage, chemical separation, ion exchange, and catalysis. 3D cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a biocompatible alternative to conventional MOFs, as they are synthesized using safer, nontoxic, or lower-toxicity components, thereby eliminating the need for potentially hazardous metals and organic linkers commonly employed in traditional MOF synthesis. In CD-MOFs, cyclodextrin molecules serve as organic linkers, while metal sources, such as KOH, NaOH, and KCl, provide the necessary metal ions for framework formation. CD-MOFs form body-centered cubic structures by binding to one of the alkali metal cations through coordination of the secondary face hydroxyl groups on the alternate d-glucopyranosyl residues. Beyond the intrinsic advantages of traditional MOFs, CD-MOFs offer additional benefits, particularly in drug delivery applications, where biocompatibility is a crucial factor. These CD-MOFs can be synthesized through various techniques, and multiple strategies can be employed for drug loading. This review comprehensively examines the synthesis of 3D CD-MOFs, their drug loading methodologies, comparative analysis of these methods in terms of advantages and limitations, and the potential of 3D CD-MOFs as drug delivery systems.