摘要
目的考察pH值对氟尿嘧啶(5-FU)从pH敏感树枝状聚合物纳米载体(mPEG-pDEA-PAMAM,PDP)中释放的影响,以及该载体制剂在不同pH值条件下对人肝癌HepG2细胞的作用。方法用HPLC分析方法测定释放介质中5-FU浓度,考察不同pH值条件下5-FU从PDP释放的特征。用不同pH值培养基体外培养人肝癌细胞株HepG2细胞,建立模拟体内肿瘤组织微环境的细胞模型,MTT法研究PDP制剂对HepG2细胞的抑制率及细胞毒性。结果 PDP在弱酸性环境(pH 6.5)中迅速释放5-FU,而在中性环境(pH 7.4)中释放很缓慢。在pH 6.5条件下,5-FU-PDP与5-FU水溶液同样对HepG2细胞生长有明显抑制作用,单用PDP没有明显细胞毒性。结论 5-FU-PDP纳米制剂具有明显pH值敏感释药的特点,能在肿瘤弱酸性环境下快速释药并发挥药效,可能成为理想的抗肿瘤药物靶向载体。
Objective To explore the effect of pH value on the release of 5-fluorouracil-loaded pH-sensitive dendrimer nanocarriers（5-FU-PDP）and the pharmacodynamics of 5-FU-PDP on HepG2 cells in different pH conditions.Methods The concentrations of 5-FU were determined by HPLC method and the release characteristics of 5-FU from nanocarriers was measured under different pH.MTT method was used to study the inhibition effect of 5-FU,5-FU-PDP and blank PDP on HepG2 cell line.Results The release of 5-FU from PDP was faster at pH 6.5 than at pH 7.4.5-FU-PDP showed singnificant inhibitory effects on growth of HepG2 cells under pH 6.5,which was similar to 5-FU aqueous solution.PDP alone showed no cytotoxicity.Conclusion The release and exerting inhibitory effects of 5-FU from PDP in tumor microenvironment showed significant pH-sensitivity.The pH-sensitive dendrimer nanocarriers may be a promising anticancer drug delivery carrier.
出处
《国际药学研究杂志》
CAS
2011年第2期148-152,共5页
Journal of International Pharmaceutical Research
基金
国家科技重大专项-综合性新药研究开发技术大平台资助项目(2009ZX09301-002)
国家自然科学基金面上项目(30772672)
