*3.2.2 CD-based polycarbonate NSs*

Polycarbonate CD-NSs are usually synthesized using active difunctional carbonyl compounds such as 1,1′-carbonyldiimidazole, triphosgene, and diphenylcarbonate (**Figure 1**, inset b). Since the resulting CD NSs present carbonate bonds between CD monomers, these NSs present short cross-linking bridges and, consequentially, a reduced swelling ability (if compared to CD- based polyesters NSs, for example) and good stability to acidic solutions. The affinity to organic molecules and the surface area are comparable to carbamate NS [46]. The ability of β-CD carbonate NS to remove from wastewater chlorinated persistent organic pollutants (also known as POP) was investigated by Trotta and Cavalli in 2009 [47]: the absorption efficiency was higher than the average of activated carbon. For the specific case of hexachlorobenzene the NS was capable of removing around 99.5% of the pollutant.

*Strategies to Develop Cyclodextrin-Based Nanosponges for Smart Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.100182*

An interesting method to evaluate the degree of cross-linking of carbonate β-CD NSs, employing infrared and Raman spectroscopy, was described by Castiglione et al. [48]. Data from spectroscopic analysis and chemical computation demonstrated a correlation between the intensity of carbonyl absorption peak and the degree of cross-linking: the degree of cross-linking increased with the amount of cross-linker, in total agreement with the stoichiometry. Dealing with sugar-based predominantly amorphous materials, the reported method represents a valid and advantageous alternative to x-ray. The crosslinking density or the amount of crosslinker, strongly influences the stiffness and elastic properties of the NSs. Rossi et al. demonstrated in their study that the mechanical features of the NSs can be easily tuned by changing the molar ratio CD/cross-linker, on the other hand, the CD used for the synthesis does not affect the mechanical properties of the final NS [34, 49].

#### *3.2.3 CD-based polyester NSs*

Ester CD-based NSs are synthesized using dianhydrides or di/polycarboxylic acids, such as pyromellitic dianhydride (PMDA), ethylenediamine- tetraacetic dianhydride (EDTA dianhydride), butanetetracarboxylic dianhydride, citric acid [46, 50].

Dissimilarly from polycarbonate and polyurethane NSs, polyester NSs are generally able to absorb remarkable amounts of water (up to 25 times/g dry sample), and form stable hydrogels. Similarly as seen before with mechanical properties, the swelling capability of the CD-NSs is generally dependent on the degree of crosslinking. The swelling capability is usually inversely proportional to the density of cross-linking: the lower the degree of cross-linking, the higher the water uptake. The structure of the material dramatically influences chemical stability. Ester NSs are subjected to hydrolysis in aqueous media more easily than polycarbonate and polyurethane NSs. The structure is remarkably interesting because of the presence of free carboxyl groups in their chemical structure, moieties that can be exploited for the absorption of cations, using the material as an ionic exchange resin.

There are in literature many examples of the formation of complexes with a metal cation. The metal ions complexation ability of pyromellitic NSs is studied by Berto et al. in for different metal cations, such as Al3+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Pd2+.

In most cases, pyromellitic NSs were found to be capable of absorbing more than 70% of the tested cation [51].

A similar test of removing heavy metals from wastewaters, crosslinking also CDs with citric acid, is performed by Rubin Pedrazzo et al. in 2019 [52]. At a metal concentration of 500 ppm, the pyromellitic NSs (substituted before absorption with Na+ ) exhibited a higher retention capacity than the citrate NSs. At lower metal concentrations (≤ 50 ppm) both the citrate and the pyromellitic NSs showed high retention capacities (up to 94% of the total amount of metal). While in the presence of interfering sea water salts, the citrate NSs were able to selectively adsorb a significantly higher amount of heavy metals than the pyromellitic NSs.

For ester NSs, similar studies of the correlation of cross-linking degree with properties are performed. Surprisingly, the highest cross-linking degree was observed in the sample prepared using the molar ratio 1: 6, CD: PMDA [53].

Higher contents of cross-linker, molar ratios like 1:8 and 1:10, led to a decrease of the degree of cross-linking; this is possibly related to the steric hindrance generated by the pyromellitic units linked to CDs. Interestingly, by working under limited dilution conditions during the reaction and with an even lower CD/cross-linker ratio (e.g., 1:2 molar ratio), it is possible to obtain a hyperbranched water-soluble polymer [54]. As already described for carbonate NSs,

Raman and Brillouin scattering experiments permitted Rossi et al. to evaluate a relationship between the mechanical characteristics of the polyester pyromellitic β-CD NS and the molar ratios CD/cross-linker: as seen before, stiffness and elasticity of the polymeric structure can be tuned by varying the amount of cross-linker [49].
