Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment

• Published in: Biochimica et biophysica acta Vol. 1840; no. 9; pp. 2730 - 2743
• Main Authors: Anitha, A., Deepa, N., Chennazhi, K.P., Lakshmanan, Vinoth-Kumar, Jayakumar, R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2014
• Subjects: 5-Fluorouracil; Animals; antineoplastic activity; bioavailability; Biological Availability; blood; cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; chitosan; Chitosan - pharmacokinetics; Chitosan - pharmacology; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; colorectal neoplasms; Combinatorial nanomedicine; crosslinking; Curcumin; Curcumin - pharmacokinetics; Curcumin - pharmacology; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; drug therapy; fluorouracil; Fluorouracil - pharmacokinetics; Fluorouracil - pharmacology; Humans; membrane potential; Membrane Potential, Mitochondrial - drug effects; Mice; mitochondrial membrane; nanomedicine; Nanoparticles; neoplasm cells; patient compliance; Pharmacokinetics; Thiolated chitosan; zeta potential; DDA; H and E; PT; RNA; COX-2; 5-Fluorouracil; TCS; EPR; CO2; FT-IR; DLS; Mw; MTT; AUC; RPM I; BSA; PPP; FdUMP; Colon cancer; TPP; OD; FBS; pH; IEC 6; Thiolated chitosan; Hb; Curcumin; HPLC; Rh 123; RNase; PBS; aPTT; ACD; 5-FU-TCS-NPs; CRC-TCS-NPs; FUTP; EDTA; NPs; HT29; CRC; DNA; PI; SEM; FdUTP; Pharmacokinetics; 5-FU; JC-1; Combinatorial nanomedicine
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.06.004

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 4days, 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. [Display omitted] •Developed a combinatorial nanomedicine of 5-FU and CRC against colon cancer•The nanomedicines produced synergistic in vitro anticancer effects.•The nanomedicine showed hemocompatible nature.•The nanomedicines showed enhanced bioavailability in a mouse model.