Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. Methods: The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. Results: According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. Conclusion: 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.
目的: 采用普朗尼克—聚乙烯亚胺纳米胶束制备高效、低毒的药物和基因输送体系。
方法: 利用小分子量的聚乙烯亚胺作为交联剂制备普朗尼克—聚乙烯亚胺纳米胶束，采用动态光散射法、芘荧光探针法分别测定聚合物的粒径、表面电动电位及临界胶束浓度，考察聚合物携带基因和药物的能力，并在细胞水平上探讨普朗尼克—聚乙烯亚胺的细胞毒性、转染效率以及对细胞内ATP和P-糖蛋白水平的影响。
结果: 成功制备了普朗尼克—聚乙烯亚胺纳米胶束，其粒径120~180 nm，表面电位+6~+9 mV，具有良好的携载基因、药物的能力。细胞生物学研究表明，普朗尼克—聚乙烯亚胺毒性较小，其中P123-PEI600基因转染效率高，并且能降低细胞内ATP和P糖蛋白水平。
结论: 普朗尼克—聚乙烯亚胺是一种良好的药物和基因输送体系，P123-PEI600是理想的可用于逆转肿瘤多药耐药的载体。