Abstract | PURPOSE: METHODS: RESULTS: The 5-FU immediate release (IR) formulations suspended in SCMC produced an immediate cytotoxic effect, whereas microspheres inhibited proliferation of tumor cells to induce apoptosis over an extended time. Minimum inhibitory concentration (IC50) values for both standard plain 5-FU and 5-FU-loaded microspheres were respectively 5.00 ± 0.004 µg/mL and 165 ± 1.9 µg/mL which showed the improved safety profile of the microsphere formulation. Tissue distribution showed high concentration of 5-FU in colon that was higher than IC50 value required to stop the growth or death of colon cancer cells from the colonic dysplasia in Duke's stage A. Significant reduction in tumor volume and multiplicity was observed with increased levels of liver enzymes in animals when treated with standard 5-FU formulation compared with 5-FU loaded microspheres. Elevated levels of serum albumin, creatinine, leukocytopenia, and thrombocytopenia were observed in animals for the standard 5-FU formulation. CONCLUSION: The PEG cross-linked CS microspheres of this study slowly released 5-FU up to 24 h to colonic region and enhanced the antitumor activity.
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Authors | Kuntal Ganguly, Anandrao R Kulkarni, Tejraj M Aminabhavi |
Journal | Drug delivery
(Drug Deliv)
Vol. 23
Issue 8
Pg. 2838-2851
(Oct 2016)
ISSN: 1521-0464 [Electronic] England |
PMID | 26530807
(Publication Type: Journal Article)
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Chemical References |
- Polyethylene Glycols
- Chitosan
- Fluorouracil
|
Topics |
- Animals
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Chemistry, Pharmaceutical
(methods)
- Chitosan
(chemistry)
- Colon
(drug effects, pathology)
- Colorectal Neoplasms
(drug therapy, pathology)
- Drug Delivery Systems
(methods)
- Fluorouracil
(pharmacology)
- HT29 Cells
- Humans
- Male
- Microspheres
- Polyethylene Glycols
(chemistry)
- Rats
- Rats, Wistar
- Tumor Burden
(drug effects)
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