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.

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.

Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition. The usage of nutraceuticals, to prevent and treat the aforementioned diseases, is limited by several features such as poor water solubility, low bioavailability, low stability, low permeability, low efficacy, etc. These downsides can be overcome by the application of the field of nanotechnology manipulating the properties and structures of materials at the nanometer scale. In this review, the linear and cyclic dextrin, formed during the enzymatic degradation of starch, are highlighted as highly promising nanomaterials- based drug delivery systems. The modified cyclic dextrin, cyclodextrin (CD)-based nanosponges (NSs), are well-known delivery systems of several nutraceuticals such as quercetin, curcumin, resveratrol, thyme essential oil, melatonin, and appear as a more advanced drug delivery system than modified linear dextrin. CD-based NSs prolong and control the nutraceuticals release, and display higher biocompatibility, stability, and solubility of poorly water-soluble nutraceuticals than the CD-inclusion complexes, or uncomplexed nutraceuticals. In addition, the well-explored CD-based NSs pathways, as drug delivery systems, are described. Although important progress is made in drug delivery, all the findings will serve as a source for the use of CD-based nanosystems for nutraceutical delivery. To sum up, our review introduces the extensive literature about the nutraceutical concepts, synthesis, characterization, and applications of the CD-based nano delivery systems that will further contribute to the nutraceutical delivery with more potent nanosystems based on linear dextrins.

Environment-friendly nanosponges, having a high content of carboxyl groups, were synthesized by crosslinking β-cyclodextrin and linecaps, a highly soluble pea starch derivative, with citric acid in water. Additionally, pyromellitic nanosponges were prepared by reacting β-cyclodextrin and linecaps with pyromellitic dianhydride in dimethyl sulfoxide and used in comparison with the citric nanosponges. After ion-exchange of the carboxyl groups H⁺ with sodium ions, the ability of the nanosponges to sequester heavy metal cations was investigated. At a metal concentration of 500 ppm, the pyromellitate nanosponges exhibited a higher retention capacity than the citrate nanosponges. At lower metal concentrations (≤50 ppm) both the citrate and the pyromellitate nanosponges showed high retention capacities (up to 94% of the total amount of metal), while, in the presence of interfering sea water salts, the citrate nanosponges were able to selectively adsorb a significantly higher amount of heavy metals than the pyromellitate nanosponges, almost double in the case of Cu²⁺.

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.