This review highlights the current status of cyclodextrin-based formulations tested in human participants, highlighting ongoing clinical research in this area. It provides a comprehensive link between the structure, properties, and clinical applications of these formulations, bridging the gap between medical theory and practical use. The aim of this work is to support the future commercialization of cyclodextrin-based therapies for patient care. Additionally, it emphasizes the need for expanded clinical investigations on cyclodextrin-based formulations, particularly cyclodextrin-based polymers, to pave the way for their successful introduction to the market. This is related to the potential of cyclodextrin-based polymers as advanced drug delivery systems, improving the therapeutic efficacy of numerous drugs. Expanding clinical trials will contribute to the optimization of cyclodextrin-based polymer synthesis, boosting their effectiveness as nanocarriers and facilitating the discovery of new disease treatments.

Cyclodextrin-based drug delivery systems provide a robust platform for designing targeted nanocarriers that efficiently encapsulate, stabilize, and deliver poorly soluble drugs to specific sites. Their unique ability to form host - guest complexes and construct supramolecular networks adorned with tailored ligands allows precise targeting of diseased areas, thereby enhancing therapeutic efficacy while minimizing systemic side effects. This review provides an overview of recent advances in cyclodextrin-based carriers for targeted drug delivery. It examines a wide array of ligand-functionalized systems, from conjugates and assemblies to branched polymers and nanosponges, organized according to their target organs, including the brain, eyes, lungs, gastrointestinal tract, liver, and breast. The discussion is grounded in an extensive literature search, highlighting strategies such as the incorporation of active targeting ligands, stimuli-responsive release mechanisms, and dual-function theragnostic platforms. Although cyclodextrin-based systems have demonstrated promising improvements in drug solubility, stability, and target specificity, challenges remain with regard to overcoming biological barriers and minimizing off-target effects. The authors believe that continued optimization of carrier design, combined with advances in targeting and stimuli-responsive technologies, will be crucial for translating these innovative systems into effective clinical therapies.

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions.

Oral drug delivery remains one of the most attractive routes for achieving safe, effective, and controlled therapeutic administration. Hydrogels represent promising systems for this purpose due to their biocompatibility, the versatility of natural and synthetic materials, and their tunable physicochemical properties. Among various candidates, dextrin-based hydrogels are particularly noteworthy, as they can respond to physiological gradients along the gastrointestinal tract, enabling targeted, site-specific, and sustained drug release for both localized and systemic treatments. This study aimed to synthesize and characterize dextrin-based hydrogels formulated from β-cyclodextrin (β-CD), KLEPTOSE® Linecaps (LC), and GluciDex®2 (GLU2) as building units, using citric acid (CA) and pyromellitic dianhydride (PMDA) as cross-linkers, for potential application in oral drug delivery systems. The obtained polymers displayed adjustable particle dimensions, pH-sensitive swelling characteristics, and an optimized cross-linking density, as calculated using the Flory–Rehner theory. Furthermore, rheological evaluations and mucoadhesion assays revealed pronounced viscoelastic behavior and strong adhesion to mucosal surfaces, confirming their suitability for oral drug delivery applications. Overall, these findings underscore the potential of dextrin-based hydrogels as mucoadhesive carriers for oral drug delivery, particularly in the treatment of neurodegenerative disorders, where they may facilitate drug transport across biological barriers and enhance therapeutic concentrations within the brain.