Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

Facile Preparation of Hierarchically Porous Aromatic-cyclodextrin Polymers and Their Application for the Selective Adsorption of Cationic Dyes

Porous β-cyclodextrin-containing materials have significant potential as adsorbents for the removal of pollutants from water. However, preparing these porous polymers in the aqueous phase is challenging. In this study, a kind of novel porous aromatic-cyclodextrin polymers (P-aro-CDPs) was designed and synthesized in aqueous solution under mild conditions by exploiting covalence-crosslinking reaction. P-aro-CDPs were characterized using a variety of methods, which revealed that P-aro-CDPs have a hierarchical porous structure, a highly negatively charged surface, and rich in hydroxyl groups. The prepared P-aro-CDPs showed excellent removal efficiency for methylene blue, with a maximum adsorption capacity of 194.17 mg g-1. The adsorption data are well fitted to the pseudo-second-order kinetic model and the Langmuir isotherm. The as-synthesized P-aro-CDPs material exhibited superior adsorption selection toward cationic dyes than anionic dyes whether in single or multicomponent systems. Further, the P-aro-CDPs adsorbent are reusable, and good performance over six adsorption–desorption cycles was demonstrated. Due to its off-the-beaten-path synthesis, low cost, excellent removal efficiency, and recyclability, P-aro-CDPs have great potential for use as an adsorbent in water-treatment applications.

Sustainable mechanochemical synthesis of β-cyclodextrin polymers by twin screw extrusion

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

Porous Multifunctional Phenylcarbamoylated-β-Cyclodextrin Polymers for Rapid Removal of Organic Pollutants

In this work, a series of porous multifunctional cyclodextrin (CD) polymers were fabricated using tetrafluoroterephthalonitrile (TFTPN) as the rigid crosslinker for the condensation of different functional phenylcarbamoylated-β-cyclodextrin derivatives to afford three preliminary polymerized adsorption materials such as poly nitrophenylcarbamoylated-β-cyclodextrin (NO2-CDP), poly trifluoromethylphenylcarbamoylated-β-cyclodextrin (F-CDP), poly chlorophenylcarbamoylated-β-cyclodextrin polymers (Cl-CDP) and a mix β- cyclodextrin polymer (X-CDP) prepared via a secondary crosslinking procedure of the above three materials. The X-CDP preparation process connects the `pre-formed nanoparticles and increases the presence of linkers inside the particles. At the same time, X-CDP exhibited porous structure with various functional groups such as nitro, chlorine, fluorine and hydroxyl. Those special characteristics render this material with good adsorption ability towards various pollutants in water, including tetracycline, ibuprofen, dichlorophenol, norfloxacin, bisphenol A, naphthol. Especially the maximum adsorption capacity for tetracycline at equilibrium reached 230.15 mg·g− 1, which is competitive with the adsorption capacities of other polysaccharides adsorbents. X-CDP removed organic contaminants much more quickly than other adsorbents, reaching almost ~ 95% of its equilibrium in only 30 s. The main adsorption process of the pollutants by X-CDP fitted the pseudo-second-order kinetic and Langmuir isotherm well, indicating that the adsorption process is monolayer adsorption. Moreover, X-CDP possessed the good reusability where the pollutant removal rate was only reduced 8.3% after five cycles.