Novel poly-β-cyclodextrin derivatives as advanced carriers for 5-fluorouracil for tumor: the impact of charge on antitumor efficiency

BACKGROUND: With the emergence of more and more cyclodextrin derivatives, cyclodextrin becomes an effective adjuvant for improving the prescription of drugs. Its application in pharmacy, especially in the sustained and controlled release, targeting, transdermal and mucosal drug delivery systems, is also being expanded and deepened. In this study, novel cyclodextrin derivatives were developed to investigate the impact of the charge on antitumor efficiency by introducing different groups (carboxymethyl or quaternary ammonium group) to poly-β-cyclodextrin (β-CD). METHODS: These novel β-CD derivatives were prepared by the nucleophilic substitution reaction and characterized by IR and (1)H NMR. Fluorouracil (5-FU) was adopted as a model drug to form inclusion compounds. The content of 5-FU in inclusion compounds was evaluated using fluorine element analysis. Also, the cytotoxicity of poly-β-CD derivatives was studied. Finally, the effect of negative and positive charges on the antitumor activity of poly-β-CD derivatives-5-FU inclusion compounds on HepG2 cancer cells was evaluated. Human liver cancer HepG2 cells (CYP3A4G/7R clone 87, RRID: CVCL_1×10) were purchased from Cell Bank, Shanghai Institutes for Biological Sciences (China). RESULTS: The results of IR and 1H NMR indicated consistently that both carboxymethyl poly-β-CD (poly-CM-β-CD) and glycidyl trimethyl ammonium chloride (GTMAC) poly-β-CD (poly-GTAC-β-CD) were successfully prepared. Fluorouracil was successfully loaded into poly-β-CD derivatives. The results of fluorine analysis indicated that the content of 5-FU in 1 g poly-β-CD, poly-GTAC-β-CD and poly-CM-β-CD was 1,214, 921 and 1,187 µg, respectively. No cytotoxicity of poly-β-CD derivatives on HepG2 cells was observed. The killing effect of poly-β-CD-5-FU on HepG2 cells was similar to that of poly-GTAC-β-CD-5-FU. Poly-CM-β-CD-5-FU had the worst killing effect on HepG2 cells. CONCLUSIONS: Charge had impact on antitumor efficiency. These novel poly-β-CD derivatives have potential applications in tumor sustained-release targeted therapy.