Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

Abstract

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.

Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems

“…The CE and K 11 values are in the same range as those obtained for other β-CyD systems [ 24 , 25 , 58 ].…”

“…Great interest is focused on the CyD-based polymers that can form water-soluble and stable NPs [ 19 ]. Furthermore, CyD-based NPs have been functionalized with vitamins, sugars, and peptides to actively target cancer cells and increase tumor internalization [ 15 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Multifunctional co-transport carriers based on cyclodextrin assembly for cancer synergistic therapy

“…The cross-linked β-CD and γ-CD polymers exhibited multiple cavities of different sizes, such that two drugs of different sizes could be transported. Bognanni et al reported preparation of cross-linked β-CD and γ-CD polymers through epichlorohydrin, wherein targeted modification of the surface of CD enabled targeting function 38 . This cross-linked polymer could assemble DOX and oxaliplatin at the same time.…”

β and γ-Cyclodextrin dimers: design, characterization and in silico studies to explore the cooperative effect of the cavities

“…21 In recent years, CyD multi-cavity systems have also been studied to improve drug inclusion. [22][23][24][25] CyD dimers have also been synthesized with linkers with different lengths and rigidity. [26][27][28][29][30][31][32] The length, flexibility, and structure of the linker connecting the two CyDs may considerably affect the thermodynamic parameters of inclusion phenomena and determine the host-guest binding modes.…”