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.
The aqueous solubility of KYNA was increased by encapsulation with β-CDNS2. • The molar ratio of CDI to β-CD affected the solubilization efficiency of nanosponges. • Higher antioxidant activity of KYNA loaded NS was achieved compared to plain KYNA. • Cell viability study showed that NS was nontoxic to SHSY-5Y human neuroblastoma cell lines. • The particle size and zeta potential of KYNA loaded NS and blank NS remained unchanged on storage.
The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different β-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29). To extend its possible use, a comparison with breast (MCF-7) cancer cell was carried out. The physicochemical properties, loading efficiency, and release kinetics of Nisin complex with nanosponges were studied. Then, tricin-SDS-PAGE electrophoresis was used to understand the effect of NSs on stability of Nisin-Z in the presence of gastric peptidase pepsin. In addition, the cytotoxicity and cell membrane damage of Nisin Z were evaluated by using the MTT and LDH assay, which was complemented via Annexin-V/ Propidium Iodide (PI) by using flowcytometry. CD-NS are able to complex Nisin-Z with an encapsulation efficiency around 90%. A protective effect of Nisin-Z complexed with CD-NSs was observed in presence of pepsin. An increase in the percentage of apoptotic cells was observed when the cancer cells were exposed to Nisin Z complexed with nanosponges. Interestingly, Nisin Z free and loaded on PMDA/CDI-NSs is more selectively toxic towards HT-29 cells than MCF-7 cancer cells. These results indicated that nanosponges might be good candidates to protect peptides and deliver drugs against intestinal cancers.
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