Preparation and Characterization of Targeted Drug Carrier Materials Poly-β-Cyclodextrin-PEG-Folate Acid

Objective: Targeted drug delivery can concentrate drugs at the lesion site and selectively kill lesion cells. Folate receptors have limited expression in human healthy cells but are over-expressing on the surface of cancer cells. Our study decided to develop one of site-specific intracellular delivery against the folate receptor. Methods: First, poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA were synthesized according to respective reaction routes and were confirmed by 1H nuclear magnetic resonance (1H NMR) and infrared spectroscopy (IR). Second, busulfan was selected as drug model and loaded into the carriers by self-assembly. The cytotoxicity of poly-β-CD-PEG-OCH3, busulfan loaded poly-β-CD-PEG-OCH3, poly-β-CD-PEG-FA and busulfan loaded poly-β-CD-PEG-FA was determined by a crystal violet stain assay. Last, The potential of poly-β-CD-PEG-FA for use in the targeting delivery of busulfan was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis in HepG2, which contain folate receptors on its surfaces. Results: poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA were successfully synthesized and proved by 1H NMR and IR. Busulfan was successfully loaded into poly β-CD-PEG-FA and poly β-CD-PEG-OCH3 and their content are 3.379 mg/g and 3.548 mg/g, respectively. Poly β-CD-PEG-OCH3 and poly β-CD-PEG-FA with the concentration between 12.5-50 μg/ml had no effect on cell survival rate of HepG2 cells but with over 100 μg/ml had a significant inhibitory effect. The MTT results revealed that in HepG2 cells, the cytotoxicity of poly-β-CD-PEG-FA loaded busulfan cells is greater than that of poly-β-CD-PEG-OCH3 loaded busulfan. Conclusion: Poly-β-CD-PEG-FA can be used as a carrier for hydrophobic anticancer chemotherapeutic drugs. After being loaded into poly-β-CD-PEG-FA, busulfan still maintained its original anticancer activity and had obvious targeted drug delivery effect on tumor cells with folate receptor over-expression.