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Bortezomib (BTZ) as an anticancer drug has been used through the injection pathway.Two types of Cyclodextrin nanosponges (CDNSs) were synthesized and studied by DLS, TEM, FTIR, and DSC instruments for BTZ delivery. Both carriers were analyzed for loading efficiencies andBoth types of CDNSs, encapsulated BTZ in their nano-porous structure, but better loading was shown in CDNS 1:4. FTIR and DSC results proved considerable encapsulation of BTZ into CDNSs. The slow and prolonged release profile was observed for CDNS 1:4 in comparison with CDNS 1:2. Based onCDNS 1:4 has the ability to be introduced as a nontoxic carrier for BTZ delivery with its high loading, controlled release manner, high cellular uptake, and permeability improvement characteristics.

Cyclodextrin nanosponges (CD-NS) are nanostructured crosslinked polymers made up of cyclodextrins. The reactive hydroxy groups of CDs allow them to act as multifunctional monomers capable of crosslinking to bi- or multifunctional chemicals. The most common NS synthetic pathway consists in dissolving the chosen CD and an appropriate crosslinker in organic polar aprotic liquids (e.g., N,N-dimethylformamide or dimethyl sulfoxide), which affect the final result, especially for potential biomedical applications. This article describes a new, green synthetic pathway through mechanochemistry, in particular via ball milling and using 1,1-carbonyldiimidazole as the crosslinker. The polymer obtained exhibited the same characteristics as a CD-based carbonate NS synthesized in a solvent. Moreover, after the synthesis, the polymer was easily functionalized through the reaction of the nucleophilic carboxylic group with three different organic dyes (fluorescein, methyl red, and rhodamine B) and the still reactive imidazoyl carbonyl group of the NS.

In this work, four types of nanosponges were prepared from pyromellitic dianhydride (PMDA) and D-glucose (GLU) with different molar ratios (1.5:1, 2:1, 2.5:1 and 3:1). The obtained PMDA/GLU nanosponges were then pyrolyzed at 800 °C for 30 min under N2 gas flow. The prepared polymeric nanosponges were investigated by FTIR spectroscopy, elemental and thermogravimetric analyses to unravel the role played by the different molar ratio of the precursors in the formation of the polymer. The pyrolyzed nanosponges were investigated by means of porosity measurements, X-ray diffraction analysis, Raman spectroscopy and high-resolution transmission electron microscopy. Notably, no significant correlation of the amounts of used precursors with the porous texture and structure was evidenced. The results corroborate that PMDA and GLU can be easily combined to prepare nanosponges and that the carbon materials produced by their pyrolysis can be associated with glassy carbons with a microporous texture and relatively high surface area. Such hard carbons can be easily obtained and shrewdly used to segregate relatively small molecules and organic contaminants, in this study methylene blue adsorption was investigated.

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.

We present a rapid and surfactant-free temperature-assisted synthesis route to prepare γ-cyclodextrin-based metal–organic framework (γ-CD-MOF). The cubic crystals of the CD-MOF with an average edge length of 10–15 µm, specific surface area of 775 m2 g−1 and total pore volume of 0.229 cm3 g−1 were synthesized in much shorter time than conventional CD-MOFs. To show the efficiency of the synthesized CD-MOF as adsorbent of gas, the uptake of CO2 at different temperature and pressure was investigated. It is shown that the CO2 uptake increases with increasing pressure and decreasing temperature. Further microgravimetric investigation on gas adsorption at low pressure demonstrated superior gas uptake (ca. 147 mg g−1) than previous reports. At the maximum equilibrium pressure, the uptake amounts of CO2 were found to be 326 and 268 mg g−1 at 303 and 323 K, respectively. The synthesized CD-MOF has great potential to be used in gas storage and separation applications.

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 &beta, cyclodextrin (&beta, 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&ndash, 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 &beta, CD-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.

Melatonin (MT) is a molecule of paramount importance in all living organisms, due to its presence in many biological activities, such as circadian (sleep–wake cycle) and seasonal rhythms (reproduction, fattening, molting, etc.). Unfortunately, it suffers from poor solubility and, to be used as a drug, an appropriate transport vehicle has to be developed, in order to optimize its release in the human tissues. As a possible drug-delivery system, β-cyclodextrin (βCD) represents a promising scaffold which can encapsulate the melatonin, releasing when needed. In this work, we present a computational study supported by experimental IR spectra on inclusion MT/βCD complexes. The aim is to provide a robust, accurate and, at the same time, low-cost methodology to investigate these inclusion complexes both with static and dynamic simulations, in order to study the main actors that drive the interactions of melatonin with β-cyclodextrin and, therefore, to understand its release mechanism.

In recent years, the development of various cyclodextrin (CD)-based nanosponges (NSs) has gained great importance in the controlled and-or targeted release of drugs due to their versatility and simple preparation. In this chapter, an introduction of different administration routes is explained. Further, different ways to obtain CD-NSs and their classification are shown with a brief explanation of the characterization of the inclusion complexes. Finally, illustrative examples in diverse processes or diseases will be reviewed and explained to demonstrate the potential of CD-NSs. Therefore, this division will serve to compile information on CD-NSs in recent years and to illustrate to readers how to generate and apply different derivatives of interest.

To date, a number of nanocarriers, either inorganic or organic, have been developed to improve the delivery and therapeutic efficacy of various drugs. Drug delivery systems have attempted to overcome the undesirable pharmacokinetic problems encountered. Among the various nanomaterials that have been designed as potential nanocarriers, cyclodextrin-based polymers are of particular interest in this review.Cyclodextrins (CD) are a class of cyclic glucopyranose oligomers, obtained from starch by enzymatic action, with a characteristic toroidal shape that forms a truncated cone-shaped lipophilic cavity. The main common native cyclodextrins are named α, β, and γ which comprise six, seven, and eight glucopyranose units, respectively. Cyclodextrins have the capability to include compounds whose size and polarity are compatible with those of their cavity.Cyclodextrin-based cross-linked polymers, often referred to as "cyclodextrin nanosponges" (CDNSs), attract great attention from researchers for solving major bioavailability problems such as inadequate solubility, poor dissolution rate, and limited stability of some agents, as well as increasing their effectiveness and decreasing unwanted side effects.Registered patents about this novel system in various fields, different pharmaceutical applications, and classes of drugs encapsulated by CDNSs are detailed. The features outlined make CDNSs a promising platform for the development of innovative and advanced delivery systems.

Carbon-based materials with different morphologies have special properties suitable for application in adsorption, catalysis, energy storage, and so on. Carbon spheres and carbon monoliths are also nanostructured materials showing promising results. However, the preparation of these materials often require the use of a template, which aggravates their costs, making the operations for their removal complex. In this work, hollow carbon microspheres and carbon monolith were successfully prepared via carbonization of hyper-crosslinked polymer based on either cyclodextrins or amylose, in a template-free way. The carbons obtained are of the microporous type, showing a surface area up to 610 m2/g, and a narrow pore distribution, typically between 5 and 15 &Aring

Cyclodextrin-based nanosponges have been found to be promising drug delivery systems. This paper investigates an application that still needs to be studied in depth, that is, the oral delivery of peptides and proteins, choosing insulin as a case study. The nanosponge was synthesized by crosslinking β-cyclodextrins with pyromellitic dianhydride, adopting a top-down approach for its subsequent formulation. A physicochemical characterization, in-vitro and in-vivo tests were carried out on the formulation developed. It was nanometric (around 250 nm) with high negative zeta potential, mucoadhesion and swelling properties, good loading capability (about 14%) and encapsulation efficiency (above 90%). The in-vitro release of insulin was negligible at a gastric pH (below 2%) while sustained at an intestinal pH, thus showing a pH-sensitive behaviour of the nanosponge. The Caco-2 cell permeability assay proved that the intestinal permeation of insulin was enhanced when loaded inside the nanosponge. The in-vivo studies confirmed the presence of insulin in rat plasma and a marked hypoglycemic effect in diabetic mice after duodenal and oral administrations, respectively. These preliminary results are encouraging with a view to continuing to study this β-cyclodextrin nanosponge technology for the oral administration of insulin and extending this approach to other proteins of pharmaceutical interest.

Cyclodextrin (CD)-based polymers are known to efficiently form molecular inclusion complexes with various organic and inorganic guest compounds. In addition, they also have a great potential as metal complexes because deprotonated hydroxyls can strongly bind metal ions under alkaline conditions. The range of environmental conditions for polycyclodextrin/metal ion complexation can be extended by the polymerization of CDs with polyacids. This article describes the preparation and characterization of a new type of poly(&beta, cyclodextrin) (Poly-&beta, CD) sub-micrometric fibers and explores their potential as metal ion sorbents. A water-soluble hyper-branched &beta, cyclodextrin polymer was blended with poly(vinyl alcohol) (PVA) and here used to improve the mechanical and morphological features of the fibers. Solutions with a different Poly-&beta, CD/PVA ratio were electrospun, and the fibers were cross-linked by a post-spinning thermal treatment at 160 &deg, C to ensure non-solubility in water. The fiber morphology was analyzed by scanning electron microscopy (SEM) before and after the curing process, and physical&ndash, chemical properties were studied by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The capability of the insoluble cyclodextrin-based fibers to remove heavy metals from wastewaters was investigated by testing the adsorption of Cu2+ and Cd2+ using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The results suggest that the poly(&beta, cyclodextrin)/poly(vinyl alcohol) sub-micrometric fibers can complex metal ions and are especially effective Cu2+ sorbents, thus opening new perspectives to the development of fibers and membranes capable of removing both metal ions and organic pollutants.

There have been many reviews of the cyclic oligosaccharide cyclodextrin (CD) and CD-based materials used for drug delivery, but the capacity of CDs to complex different agents and their own intrinsic properties suggest they might also be considered for use as active drugs, not only as carriers. The aim of this review is to summarize the direct use of CDs as drugs, without using its complexing potential with other substances. The direct application of another oligosaccharide called cyclic nigerosyl-1,6-nigerose (CNN) is also described. The review is divided into lipid-related diseases, aggregation diseases, antiviral and antiparasitic activities, anti-anesthetic agent, function in diet, removal of organic toxins, CDs and collagen, cell differentiation, and finally, their use in contact lenses in which no drug other than CDs are involved. In the case of CNN, its application as a dietary supplement and immunological modulator is explained. Finally, a critical structure–activity explanation is provided.

In this work, the increase of the Caenorhabditis elegans (C. elegans) lifespan extension using hyper-branched cyclodextrin-based nanosponges (CD-NS) complexing oxyresveratrol (OXY), and the possible inhibition of C. elegans phosphodiesterase type 4 (PDE4) were evaluated. The titration displacement of fluorescein was used to calculate the apparent complexation constant (KF) between CD-NS and OXY. Moreover, PDE4 was expressed in E. coli, purified and refolded in presence of cyclodextrins (CDs) to study its possible inhibition as pharmacological target of OXY. The apparent activity was characterized and the inhibitory effect of OXY on PDE4 displayed a competitive in vitro inhibition corroborated in silico. A maximum increase of the in vivo life expectancy of about 9.6% of using OXY/CD-NS complexes in comparison with the control was obtained, in contrast to the 6.5% obtained with free OXY. No effect on lifespan or toxicity with CD-NS alone was found. These results as a whole represent new opportunities to use OXY and CD-NS in lifespan products.

Natural deep eutectic solvents (NADESs) represent an environmentally friendly replacement for petroleum-based solvents; for this reason, they are a major field of research which aims to reduce the industrial emissions, looking forward to greener processes. Besides, beta cyclodextrin (βCD)-based polymers are a class of materials widely exploited for the controlled release of drugs and the adsorption of undesired substances in many pharma, food, and environmental applications. However, most syntheses of βCD-based polymers require the use of organic solvents or toxic reactants; hence, describing a green way to obtain such a class of materials would make the process more sustainable and suitable for eco-friendly scaling-up. In this work, the synthesis of water-soluble βCD-based polymers characterized by molecular weight ranging from 15 kDa to 19 kDa has been reported, using 1 : 1, 1 : 1.5, and 1 : 2 mol : mol choline chloride/citric acid NADESs as a solvent. The peculiar structure displayed by the resulting polymer allowed the latter to be cured into a βCD-based nanosponge, turning its structure from a water-soluble to cross-linked one. Eventually, the obtained βCD-based nanosponges displayed positive ζ-potential values ranging up to +20 mV, related to the presence of quaternary ammonium functions. This positive charge obtained was dependent on the choline chloride/citric acid molar ratio chosen for the NADES preparation, and further confirmed by adsorption and release studies with charged probe molecules.

The design and structural optimisation of a novel polysaccharide-based nanomaterial for the controlled and sustained release of doxorubicin are here reported. A cross-linked polymer was obtained by reacting a tetraglucose, named cyclic nigerosyl-1-6-nigerose (CNN), with pyromellitic dianhydride. The cross-linking reaction formed solid nanoparticles, named nanosponges, able to swell as a function of the pH. Nanoparticle sizes were reduced using High Pressure Homogenization, to obtain uniform nanosuspensions. Doxorubicin was incorporated into the CNN-nanosponges in a good extent. DSC and solid state NMR analyses proved the drug interaction with the polymer matrix. In vitro studies demonstrated pH-dependent slow and prolonged release kinetics of the drug from the nanoformulation. Doxorubicin-loaded CNN-nanosponges were easily internalized in A2780 cell line. They might considered an intracellular doxorubicin reservoir, able to slowly release the drug over time. CNN-nanosponges may be promising biocompatible nanocarriers for the sustained delivery of doxorubicin with potential localised application in cancer treatments.

In this work, the interaction between Kynurenic acid (KYNA) and several natural and modified cyclodextrins (CDs) is carried out. Among all the CD tested, HPβ-CD showed the strongest complexation constant (KF), with a value of 270.94 ± 29.80 M−1. Between natural (α- and β-) CDs, the complex of KYNA with β-CD was the most efficient. The inclusion complex of KYNA with CDs showed a strong influence of pH and temperature. The KF value decreased at high pH values, when the pKa was passed. Moreover, an increase of the temperature caused a decrease in the KF values. The thermodynamic parameters of the complexation (ΔH°, ΔS° and ΔG°) were studied with negative entropy, enthalpy and spontaneity of the process at 25 °C. Moreover, the inclusion complex was also characterized using FTIR and TGA. Finally, molecular docking calculations provided different interactions and their influence in the complexation constant.

Ailanthone, a quassinoid from Ailanthus altissima (Mill.) Swingle, is a natural herbicide, whose use is limited by its low persistence and rapid degradation in organic substrates. Dextrin-based nanosponges (NSs) are polymers with a cage-like structure that can complex several molecules, acting as carriers or protectors. Their encapsulation efficiency can be exploited in numerous applications. Hence this study explored at first the biological activity of eight different dextrin-based NSs, synthesized with 1,1′-carbonyldiimidazole (CDI) or pyromellitic dianhydride (PYRO) (αNS-CDI, βNS-CDI, γNS-CDI, LC NS-CDI, αNS-PYRO, βNS-PYRO, γNS-PYRO, and LC NS-PYRO), towards two model species (Lepidium sativum L. and Raphanus sativus L.) in filter paper under controlled conditions in laboratory. Then, the selected dextrin-based NSs were loaded with ailanthone and applied in the concentration of 7.5 or 30 mg L−1 of ailanthone in pre-emergence on the same species, initially on filter paper and subsequently on cultivation substrate for horticulture. In all three bioassays, the number of germinated seeds and the length of developed roots and hypocotyls were evaluated. In the first bioassay, the results showed that five dextrin-based NSs promoted the germination and root elongation, thus counteracting the herbicidal effect of ailanthone. Hence, three selected formulations (αNS-CDI, γNS-CDI, and LC NS-CDI) were loaded with ailanthone, with γNS-CDI providing the highest loading capacity (1.36%) and encapsulation efficiency (55.15%). In the second bioassay, the phytotoxic activity of ailanthone was strengthen by dextrin-based NSs, always stronger by at least 58% than the pure compound across 30 days in paper, without differences between formulations. In the third bioassay, loading ailanthone in γNS-CDI also prolonged its herbicidal activity, still reducing to only 20% the germination and growth of garden cress and radish 30 and 20 days after treatment, respectively. Overall, results demonstrated that dextrin-based nanosponges can be proposed as suitable carriers in the formulation of ailanthone-based herbicide. Their use both increased and extended the phytotoxic activity of ailanthone, leading to the possibility of reducing the amount applied for each treatment, or reducing the number of herbicide treatments.

Li-O2 batteries represent a promising rechargeable battery candidate to answer the energy challenges our world is facing, thanks to their ultrahigh theoretical energy density. However, the poor cycling stability of the Li-O2 system and, overall, important safety issues due to the formation of Li dendrites, combined with the use of organic liquid electrolytes and O2 cross-over, inhibit their practical applications. As a solution to these various issues, we propose a composite gel polymer electrolyte consisting of a highly cross-linked polymer matrix, containing a dextrin-based nanosponge and activated with a liquid electrolyte. The polymer matrix, easily obtained by thermally activated one pot free radical polymerization in bulk, allows to limit dendrite nucleation and growth thanks to its cross-linked structure. At the same time, the nanosponge limits the O2 cross-over and avoids the formation of crystalline domains in the polymer matrix, which, combined with the liquid electrolyte, allows a good ionic conductivity at room temperature. Such a composite gel polymer electrolyte, tested in a cell containing Li metal as anode and a simple commercial gas diffusion layer, without any catalyst, as cathode demonstrates a full capacity of 5.05 mAh cm−2 as well as improved reversibility upon cycling, compared to a cell containing liquid electrolyte.

β-Cyclodextrin polymer, namely nanosponges (NSs), were synthesized using two cross-linkers: 1,1′-carbonyldiimidazole (CDI) and pyromellitic dianhydride (PMDA). The synthesized NSs were complexed with N,N-diethyl-meta-toluamide (DEET) and, after complex characterization, the NSs cross-linked with CDI were found more effective than those cross-linked with PMDA in terms of encapsulation efficiency and loading capacity. The CDI-NSs were dispersed in a polyacrylic resin, which was thermally polymerized on a polyester fabric surface. The fabric functionalization was evaluated through quantification of DEET extracted from the polyester fabrics, before and after three washing cycles. The results showed that encapsulation into NSs prolongs the persistence of DEET on polyester fabrics.

Environment-friendly nanosponges, having a high content of carboxyl groups, were synthesized by crosslinking &beta, cyclodextrin and linecaps, a highly soluble pea starch derivative, with citric acid in water. Additionally, pyromellitic nanosponges were prepared by reacting &beta, 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 (&le, 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+.

Aim: In this study, a nanosponge structure was synthesised with capability of encapsulating curcumin as a model polyphenolic compound and one of the herbal remedies that have widely been considered...

Kynurenic acid demonstrates antioxidant, neuroprotective and free radical scavenging properties. However, low aqueous solubility of kynurenic acid limits its therapeutic activity. In the present study, cyclodextrin nanosponges were used to improve the solubility and therapeutic activity of kynurenic acid. The formation of kynurenic acid loaded nanosponge was confirmed by different characterization techniques. The solubility of kynurenic acid was significantly increased with nanosponge (111.1 μg/ml) compared to free kynurenic acid (16.4 μg/ml) and β-cyclodextrin (28.6 μg/ml). High drug loading (19.06%) and encapsulation efficiency (95.31%) were achieved with NS. The particle size and zeta potential of kynurenic acid loaded nanosponge was around 255.8 nm and −23 mV respectively. Moreover, higher solubilization of kynurenic acid loaded nanosponge produced better antioxidant activity compared to free kynurenic acid. The kynurenic acid loaded nanosponge and blank nanosponge were found nontoxic in the cytotoxicity assay. Thus, these studies demonstrated that nanosponges can be used as a carrier for the delivery of kynurenic acid.

In this work, we exploit the antimicrobial properties of coriander essential oil (CEO) incorporated in dextrin-derived nanosponges to create a stable controlled release system. Nanosponges (CD-NS) were loaded with CEO, characterized by means of scanning and transmission electron microscopy (SEM and TEM) and X-ray diffraction (XRD), and tested for their antimicrobial activity against foodborne pathogens. A head-space-solid phase microextraction coupled to gas chromatography (HS-SPME-GC–MS) method to assess CEO five major compounds was successfully validated. CEO loading was dependent on solvent and CD-NS choice. Additionally, CEO incorporation in CD-NS increased its crystallinity. While β-CD-NS and HP-β-CD:β-CD-NS incorporated higher CEO amounts than α-NS, the later proved more effective regarding their antimicrobial activity. CEO-α-CD-NS and CEO-HP-β-CD:β-CD-NS revealed a predominant bactericidal activity, CEO-β-CD-NS only exhibited a bacteriostatic action. We describe, for the first time, the incorporation of whole EOs in CD-NS and their ability to provide a controlled oil release, especially in the cases of β-derived-CD-NS, while inhibiting bacterial growth, creating a potential new strategy to overcome the poor efficacy of current antimicrobial food packaging. Industrial relevance The manufacturing of antimicrobial food packages is still hindered by the problems posed by its lack of efficiency and poor compound stability. The fact that the cyclodextrin nanosponges synthetized in this work can provide a controlled release of antimicrobial active agent, in this case, coriander essential oil while preserving this compound's antimicrobial activity against foodborne pathogens can open the doors for its use in antimicrobial food packaging films. Furthermore, given that cyclodextrin nanosponges are stable at temperatures over 200 °C, gives the packaging industry the opportunity of incorporating this technology during the extrusion process of film making, making the process of active packaging materials cheaper, faster and more readily scalable.

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166 mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1 N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

The incidence of heart failure (HF) is increasing worldwide and myocardial infarction (MI), which follows ischemia and reperfusion (I/R), is often at the basis of HF development. Nanocarriers are interesting particles for their potential application in cardiovascular disease. Impaired drug delivery in ischemic disease is challenging. Cyclodextrin nanosponges (NS) can be considered innovative tools for improving oxygen delivery in a controlled manner. This study has developed new α-cyclodextrin-based formulations as oxygen nanocarriers such as native α-cyclodextrin (α-CD), branched α-cyclodextrin polymer (α-CD POLY), and α-cyclodextrin nanosponges (α-CD NS). The three different α-CD-based formulations were tested at 0.2, 2, and 20 µg/mL to ascertain their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) in vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to normoxia (20% oxygen) or hypoxia (5% CO2 and 95% N2). The different formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15% to 30%) when compared to samples devoid of oxygen. Moreover, their application at the beginning of reoxygenation induced a considerable reduction in cell death (12% to 20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment.

Cyclodextrin-based nanosponges (CD-NSs) are insoluble, highly cross-linked 3D network polymers used in several scientific and technological fields, the main area of investigation concerns the pharmaceutical applications, in which CD-NSs have been mostly employed as drug delivery systems. CD-NSs can be generally grouped into four consecutive generations, taking into account their chemical composition and properties. The 1st generation of NSs are plain nanosponges, subdivided into four main types: urethane, carbonate, ester and ether NSs, depending on the chemical nature of the functional group connecting the CD to the cross-linker. The 2nd generation of NSs are modified nanosponges characterized by specific properties, such as fluorescence and electric charge. The 3rd generation of NSs is represented by stimuli-responsive CD polymers, which are able to modulate their behavior according to external variations in the environment, such as pH and temperature gradients, oxidative/reducing conditions, and finally the 4th generation of NSs, a new family of molecularly imprinted CD polymers (MIPs), exhibiting a high selectivity towards specific molecules. The following review focuses on the evolution of cyclodextrin nanosponges, listing some examples of each generation.

In light of the recent development of new soft materials, nanostructured self-assembled systems have attracted attention in a variety of technological fields of high social impact. Cyclodextrin nanosponges (CDNS) represent a new and highly versatile class of cross-linked cyclodextrin (CD)-based nanoporous polymers. Their intriguing properties, including safety, biodegradability, negligible toxicity, marked swelling behavior, superior inclusion capability with respect to native CD, are the bases for potential for applications in drug delivery, tissue engineering and regenerative medicine. Areas covered: We report on the state-of-art concerning a detailed characterization of structural and dynamical features of CDNS explored by the combined use of different and complementary techniques, such as Fourier transform infrared absorption in attenuated total reflectance geometry (FTIR-ATR) and Raman spectroscopies, and high resolution magic angle spinning (HR-MAS) NMR spectroscopy. The ambitious objective is to furnish an exhaustive survey of the role played by hydrophobic and hydrophilic groups within the cross-linked network, in dry and swollen states, in determining the macroscopic functional features of CDNS. Expert opinion: The reported results may significantly contribute in the rational design and optimization of new stimuli-responsive systems exhibiting tunable inclusion/release properties, adapted to the therapeutic demands of pathology.

Linear maltodextrin (LM) was cross-linked by pyromellitic dianhydride to afford LM polymers of different cross-linking degrees. When soaked in water, these cross-linked LM polymers (nanosponges (NSs)), evolved into several phases from sol to suspension, then to flowing gel, and finally to rigid gel with an increase in their content. Enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to chiral (E)-isomer (1E), which was employed as a benchmark reaction to quantitatively assess the environmental-to-molecular chirality transfer process, was performed in aqueous media containing these pyromellitate-crosslinked LM-NSs in different phases. The enantiomeric excess (ee) of 1E obtained was relatively insensitive to the phases at least up to the flowing gel phase, but became highly sensitive in the rigid gel phase, exhibiting an abrupt drop in the early rigid gel phase followed by a rapid recovery in the late rigid gel phase. A comparison with the phase-dependent ee profiles previously reported for similar pyromellitate-crosslinked cyclodextrin (CD)- and cyclic nigerosylnigerose (CNN)-NSs revealed that the chiral void space created around the pyromellitate linker in NS is responsible for the dramatic changes in ee in the rigid gel phase, whereas the inherent host cavity in CD/CNN plays only limited roles in the supramolecular photochirogenesis mediated by the sensitizer-crosslinked NSs. The latter insight allows us to further expand the applicable range of the present concept and methodology by employing a much wider variety of oligosaccharides as well as substrates and sensitizing cross-linkers.

Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have been used as delivery system of different drugs. In this work, new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer condensation method to release the calcium in controlled manner in the treatment of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly spherical shape, porous nature and mean particle size of about 400 nm. Zeta potentials of the nanosponges were sufficiently high to obtain stable formulations. The encapsulation efficiencies of calcium in nanosponge formulations were found to be 81-95%. The moisture contents of the nanosponges were in the range of 0.1-0.7%. The optimized formulation produces enteric and controlled release kinetics of calcium in the management and treatment of hyperphosphatemia. It was also observed that calcium ions bound efficiently to free phosphate in a pH-dependent fashion especially at pH 7. In accelerated stability study no significant changes occurred in physical appearance, size and nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed that calcium carbonate was encapsulated in nanosponges structure.

A β-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (βNS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of βNS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of βNS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in βNS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the βNS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without βNS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that βNS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable βNS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin.

A series of carbons were prepared by pyrolysis of hyper cross-linked cyclodextrins, also known as nanosponges (NS). Pore structure analysis showed that pores with a range size of 5–16 A can be created from β-CD an NS cross-linked with pyromellitic dianhydride (PY). NS cross-linked with hexamethylene diisocyanate (HD) was ineffective to produce pores. SEM observation reveals a peculiar morphology of the PY-NS carbon, made of perfectly spherical hollow particles. TGA and FT-IR studies demonstrate that the PY-NS is the more efficient carbon precursor.

Biofunctional textiles are a new category of advanced materials which combine conventional textiles with advanced drug delivery systems to obtain fabrics able to release active principles through skin. The work presents the synthesis of hyper cross-linked β-cyclodextrins nanosponges with the carbonyl group acting as bridge between cyclodextrin molecules. The result of the synthesis is a 3-D porous structure, where melatonin molecules have been complexed. The complex has been characterized by elemental analysis, DSC, SEM, XRD and FT-IR spectroscopy and the results confirm that melatonin interacts with the synthesized nanosponge at molecular level. Melatonin loaded nanosponges have been dispersed on cotton fibres, which have proved to be a suitable substrate for durable nanosponge adsorption. The in vitro release tests from the funtionalized fabrics have shown a zero order kinetics, which is typical of a reservoir diffusion controlled system.

A novel oxygen selective highly hydrophobic membrane is prepared by non-solvent induced phase separation in which a dextrin-based nanosponge is incorporated into a poly(vinylidene fluoride co-hexafluoropropylene) (PVDF-HFP) matrix. The membrane presents high capability to entrap moisture from air as well as good hydrophobic behaviour. The membrane was assembled in a pouch type Li–air cell, which was cycled in a galvanostatic mode at curtailed capacity, in air with 17% relative humidity (RH). Owing to the protection of the membrane, the Li–air cell was able to discharge and re-charge for approximately 145 cycles, which correspond to about 1450 h of cell operation.

Although the roots of molecularly imprinted polymers lie in the beginning of 1930s in the past century, they have had an exponential growth only 40–50 years later by the works of Wulff and especially by Mosbach. More recently, it was also proved that molecular imprinted membranes (i.e., polymer thin films) that show recognition properties at molecular level of the template molecule are used in their formation. Different procedures and potential application in separation processes and catalysis are reported. The influences of different parameters on the discrimination abilities are also discussed.

Electrospun beta-cyclodextrin (&beta, CD)-based polymers can combine a high surface-to-volume ratio and a high loading/controlled-release-system potential. In this work, pyromellitic dianhydride (PMDA)/&beta, CD-based nanosponge microfibers were used to study the capability to host a common insect repellent (N,N-diethyl-3-toluamide (DEET)) and to monitor its release over time. Fibrous samples characterized by an average fibrous diameter of 2.8 &plusmn, 0.8 &micro, m were obtained and subsequently loaded with DEET, starting from a 10 g/L diethyl ether (DEET) solution. The loading capacity of the system was assessed via HPLC/UV&ndash, Vis analysis and resulted in 130 mg/g. The releasing behavior was followed by leaving fibrous DEET-loaded nanosponge samples in air at room temperature for a period of between 24 h and 2 weeks. The releasing rate and the amount were calculated by thermogravimetric analysis (TGA), and the release of the repellent was found to last for over 2 weeks. Eventually, both the chemical composition and sample morphology were proven to play a key role for the high sample loading capacity, determining the microfibers&rsquo, capability to be applied as an effective controlled-release system.

Poly(vinylacohol) (PVA) is a versatile polymer capable of forming hydrogels useful in a wide range of applications. Hydrogels based on cross-linking of PVA with borax, and able to incorporate organic solvents, have been used in the field of cultural heritage as tool for cleaning the surfaces. Poly(ethylenoxide) (PEO) has been introduced in the formulations of PVA-borax, with the aim of increasing the gel compatibility with organic solvents and of improving the mechanical properties of the materials. The formulations were investigated with rheological characterization, solvent loss measurements and study of the free water through the determination of the Free Water Index. The PEO molecules do not participate in the formation of the network but have been found to be responsible for a decrement of the storage moduli, explained by a spacing between crosslinks and the partial disentanglement of the PVA chains. At the same time PEO produces in the gel an increase of the apparent relaxation time, thus stabilizing the dispersions and enhancing their ability to maintain the shape. Cleaning tests for removal of an acrylic coating on limestone have been also successfully performed.

Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

The design of new nanocarriers as a strategy for the delivery of anti-cancer drugs offers a potential platform to overcome some limitations of current clinical treatments and to achieve targeted release into tumour tissues. Cyclodextrin-based nanosponges are a novel nanosized delivery system composed of hyper-cross-linked cyclodextrins connected in a three-dimensional network. They form porous nanoparticles with sizes lower than 500 nm, spherical shape and negative surface charge. They show a good capacity for incorporating small molecules, macromolecules, ions and gases within their structure.This review will describe some applications of cyclodextrin-based nanosponges as carriers for anticancer drugs. Recent smart nanosponges, able to be responsive to an external stimulus, will be also discussed. In vitro and in vivo experimental results, obtained with currently used molecules, such as paclitaxel, doxorubicin, 5-fluorourcil and tamoxifen, will be shown.Cyclodextrin-based nanosponges can be considered a challenging technology for the development of innovative formulations, suitable for various administration routes for anti-cancer drugs.

Cyclodextrin nanosponges bearing carboxylate groups have been prepared by crosslinking β-cyclodextrin with pyromellitic dianhydride to form a carboxylic acid terminated nanoporous material. The surface of the particles was covalently modified with an anti-IgG antibody and then loaded with horseradish peroxidase. The structures of unmodified and protein modified nanosponge particles were investigated by Raman spectroscopy and imaging methods. Confocal microscopy indicates that the antibody is located in the outside of the particle while HRP is encapsulated in the inner part. The possibility to use these modified nanosponges as a signal enhancement tool in enzyme-linked colorimetric and electrochemical assays was evaluated using a sandwich format comprising immobilised gliadin as an antigen, a target anti-gliadin antibody and an anti-IgG antibody conjugated to the enzyme-loaded nanosponge immunoconjugates.

Enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene were performed by using the pyromellitate-linked cyclodextrin network polymer, termed “cyclodextrin nanosponge (CDNS)”, as a supramolecular sensitizing host. The photochirogenic behavior of the nanosponges incorporating β- or γ-cyclodextrin was significantly different from that reported for the conventional sensitizer-appended monomeric cyclodextrins, affording chiral (E)-cyclooctene and (E,Z)-cyclooctadiene in enantiomeric excesses critically dependent on the solution pH and solvent composition employed, revealing the active roles of chiral void spaces of CDNS in the photochirogenic reaction.

Mixed micellar systems containing polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymers and TiO2 nanoparticles in a solvent/non-solvent pair were prepared and used as scaffolds in order to obtain nanostructured titania films. The inorganic content was varied in a wide range of compositions, focusing on micellar systems with PS cores and PEO/TiO2 coronas. The spherical-to-cylindrical micelle transition was achieved by adding a small amount of homopolymer of the same nature of the core-forming block. Thin PS-b-PEO/TiO2 hybrid films with different morphologies were prepared by spin coating micellar solutions and were transformed into the corresponding titania films by thermal treatments. The degradation of the polymer template and the simultaneous crystallization of titanium dioxide were carried out without collapsing of the nanostructures. As a final result porous and worm-like nanostructured titania films were obtained.

Pyromellitate-bridged cyclodextrin nanosponges (CDNSs) evolved from sol into gel state upon gradual increase of the concentration from 0.2 to 2000 mg mL(-1) in water. The enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene sensitized by CDNS at various concentrations were critically affected by the phase transition of CDNS to afford the corresponding (E)- and (E,Z)-isomers in the highest enantiomeric excesses in the gel state.