Nowadays, research in the field of nanotechnology and nanomedicine has become increasingly predominant, focusing on the manipulation and development of materials on a nanometer scale. Polysaccharides have often been used as they are safe, non-toxic, hydrophilic, biodegradable and are low cost. Among them, starch derivatives and, in particular, cyclodextrin-based nanosponges (CD NSs) have recently emerged due to the outstanding properties attributable to their peculiar structure. In fact, alongside the common polysaccharide features, such as the presence of tunable functional groups and their ability to interact with biological tissues, thus giving rise to bioadhesion, which is particularly useful in drug delivery, what makes CD NSs unique is their three-dimensional network made up of crosslinked cyclodextrin units. The name “nanosponge” appeared for the first time in the 1990s due to their nanoporous, sponge-like structure and responded to the need to overcome the limitations of native cyclodextrins (CDs), particularly their water solubility and inability to encapsulate charged and large molecules efficiently. Since CD NSs were introduced, efforts have been made over the years to understand their mechanism of action and their capability to host molecules with low or high molecular weight, charged, hydrophobic or hydrophilic by changing the type of cyclodextrin, crosslinker and degree of crosslinking used. They enabled great advances to be made in various fields such as agroscience, pharmaceutical, biomedical and biotechnological sectors, and NS research is far from reaching its conclusion. This review gives an overview of CD NS research, focusing on the origin and key points of the historical development in the last 50 years, progressing from relatively simple crosslinked networks in the 1960s to today’s multifunctional polymers. The approach adopted in writing the present study consisted in exploring the historical evolution of NSs in order to understand their role today, and imagine their future.

The cross-linking density influences the physicochemical properties of cyclodextrin-based nanosponges (CD-NSs). Although the effect of the cross-linker type and content on the NSs performance has been investigated, a detailed study of the cross-linking density has never been performed. In this contribution, nine ester-bridged NSs based on β-cyclodextrin (β-CD) and different quantities of pyromellitic dianhydride (PMDA), used as a cross-linking agent in stoichiometric proportions of 2, 3, 4, 5, 6, 7, 8, 9, and 10 moles of PMDA for each mole of CD, were synthesized and characterized in terms of swelling and rheological properties. The results, from the swelling experiments, exploiting Flory–Rehner theory, and rheology, strongly showed a cross-linker content-dependent behavior. The study of cross-linking density allowed to shed light on the efficiency of the synthesis reaction methods. Overall, our study demonstrates that by varying the amount of cross-linking agent, the cross-linked structure of the NSs matrix can be controlled effectively. As PMDA βCD-NSs have emerged over the years as a highly versatile class of materials with potential applications in various fields, this study represents the first step towards a full understanding of the correlation between their structure and properties, which is a key requirement to effectively tune their synthesis reaction in view of any specific future application or industrial scale-up.

Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation. Based on numerous studies reviewed, the drug appeared more active in a complex form. This review aims to summarize the performance of CDs and CD-based polymers as activity enhancers. Accordingly, the review is divided into two parts, i.e., the effect of CDs as active drugs and as enhancers in antimicrobials, antivirals, cardiovascular diseases, cancer, neuroprotective agents, and antioxidants.

Natural deep eutectic solvents (NADES) represent an environmentally-friendly replacement of petroleum-based solvents, for this reason, they are a major field of research which aims to reduce the industrial emissions, looking...

Cyclodextrin nanosponges (CD-NS) are cross-linked cyclodextrin polymers characterized by a nanostructured three-dimensional network. CD-NSs in the last years found many different applications in the pharmaceutical field for the controlled release of drugs and for the absorption of undesired substances from physiological media, food, and wastewater. Most of CD-NS syntheses involve the solubilization of the chosen CD in closed batch, using a suitable organic polar aprotic liquid, which may affect potential environmental or biomedical applications. Since the research is now moving towards more sustainable approaches, new and greener syntheses of CD-NS are now being developed. Here, it is reported a new eco-friendly and efficient synthesis of nanosponges through mechanochemistry. Mechanochemistry involves the application of mechanical forces to drive and control chemical reactions by transferring energy to chemical bonds. The mechanochemical approach involves the use of a twin-screw extruder (TSE) as a chemical reactor: TSE are capable of fine temperature control and, furthermore, TS Extrusion is a continuous process and not a batch process. Among the many available CD-NS syntheses, we tested our solvent-free approach on a β-CD/citric acid (CA) system. Moreover, using TSE, the same polymer was obtained in a considerably shorter time. The so obtained NSs were used for the adsorption and removal of probe molecules, in comparison with NSs prepared by cross-linking β-CD with CA in batch. Graphical Abstract