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  • Title: Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.
    Author: Anitha A, Deepa N, Chennazhi KP, Lakshmanan VK, Jayakumar R.
    Journal: Biochim Biophys Acta; 2014 Sep; 1840(9):2730-43. PubMed ID: 24946270.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
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