Udofot Ofonime, Affram Kevin, Smith Taylor, Tshabe Bulumko, Krishnan Sunil, Sachdeva Mandip, Agyare Edward
Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Nat Sci. 2016;2(1).
The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model. Mean size of pHLNp-5-FU was 164.3 ± 8.4 nm with entrapment efficiency (E.E) of 54.17%. While cytotoxicity of 5-FU and pHLNps-5-FU showed a strong dose-dependent, pHLNps-5-FU proved to be more effective (2-3 fold high) than that of 5-FU against HCT-116 cells. Pharmacokinetic study showed a prolonged plasma circulation of pHLNps-5-FU and a more significant body exposure while accumulation of pHLNps-5-FU in tumor was significantly higher than that of free 5-FU. Further, the efficacy of pHLNps-5-FU, was greater than free 5-FU at equivalent 5-FU dose. The study suggests that pHLNps may be an effective drug delivery system to enhance the anticancer activity of 5-FU against colorectal tumor growth.
本研究的目的是调查包裹5-氟尿嘧啶（5-FU）的pH敏感脂质体纳米颗粒与表面修饰的抗表皮生长因子受体（EGFR）抗体（pHLNps-5-FU）递送系统的药代动力学和疗效。在体外测定了5-FU和pHLNps-5-FU对HCT-116细胞的细胞毒性。在HCT-116皮下小鼠模型中测定了给药的5-FU和pHLNps-5-FU的生物分布和药代动力学参数以及5-FU和pHLNps-5-FU的疗效。pHLNp-5-FU的平均粒径为164.3±8.4nm，包封率（E.E）为54.17%。虽然5-FU和pHLNps-5-FU的细胞毒性呈现出强烈的剂量依赖性，但pHLNps-5-FU对HCT-116细胞的效果比5-FU更有效（高2-3倍）。药代动力学研究表明，pHLNps-5-FU的血浆循环时间延长，体内暴露更显著，同时pHLNps-5-FU在肿瘤中的蓄积明显高于游离5-FU。此外，在等效的5-FU剂量下，pHLNps-5-FU的疗效大于游离5-FU。该研究表明，pHLNps可能是一种有效的药物递送系统，可增强5-FU对结直肠癌生长的抗癌活性。
