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

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...

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Veröffentlicht in:Biochimica et biophysica acta Jg. 1840; H. 9; S. 2730 - 2743
Hauptverfasser: Anitha, A., Deepa, N., Chennazhi, K.P., Lakshmanan, Vinoth-Kumar, Jayakumar, R.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 01.09.2014
Schlagworte:
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
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0304-4165
0006-3002
1872-8006
DOI:10.1016/j.bbagen.2014.06.004