Anitha A, Deepa N, Chennazhi K P, Lakshmanan Vinoth-Kumar, Jayakumar R
Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
Biochim Biophys Acta. 2014 Sep;1840(9):2730-43. doi: 10.1016/j.bbagen.2014.06.004. Epub 2014 Jun 17.
Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model.
CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC.
The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU.
To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo.
The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.
评估载有姜黄素/5-氟尿嘧啶的硫醇化壳聚糖纳米颗粒（CRC-TCS-NPs/5-FU-TCS-NPs）对结肠癌细胞的联合抗癌作用，并分析CRC-TCS-NPs/5-FU-TCS-NPs在小鼠模型中的药代动力学和生物分布。
通过离子交联制备CRC-TCS-NPs/5-FU-TCS-NPs。通过不同检测方法证实了该纳米药物的体外联合抗癌作用。此外，使用高效液相色谱法在瑞士白化小鼠中进行药代动力学和生物分布分析。
5-FU-TCS-NPs（尺寸：150±40nm，zeta电位：+48.2±5mV）和CRC-TCS-NPs（尺寸：150±20nm，zeta电位：+35.7±3mV）被证明与血液相容。在pH4.5和7.4条件下的体外药物释放研究显示，在4天的时间内呈现持续释放曲线，两个体系在酸性pH下均表现出更高的释放率。使用MTT、活/死、线粒体膜电位和细胞周期分析测量法对结肠癌细胞（HT29）进行的体外联合抗癌作用证实了抗癌作用增强（2.5至3倍）。药代动力学研究证实，与单纯的CRC和5-FU不同，5-FU和CRC的血浆浓度在72小时内有所提高。
总之，5-FU-TCS-NPs和CRC-TCS-NPs的组合在体外对结肠癌细胞显示出增强的抗癌作用，并提高了药物在体内的生物利用度。
联合纳米药物增强的抗癌作用在减少5-FU剂量方面具有优势，从而提高了结直肠癌病例的化疗疗效和患者依从性。
