Abstract
Objective: 5-Fluorouracil (5-FU) and celecoxib (Cel) combination offered additive effect in the treatment of colon cancer. However, physicochemical and biopharmaceutical attributes of both drugs deliver suboptimal concentration at the site of action. The objective of the current study is the development of a microparticulate drug delivery system loaded with a combination of 5-FU and Cel to achieve prolonged drug delivery in colon cancer.
 Methods: 5-FU and Cel combination were loaded in Eudragit coated chitosan (CH) microspheres (MSs) and characterized.
 Results: The average particle size of the MSs was in the range of 2.7±0.9μm to 4.8±1.1μm. A substantial drug encapsulation efficiency of 71.30±2.3% as obtained for 5-FU as compared to 35.20±1.9% of Cel in the tailored microparticles. The drug loading capacity of 6.5 mg/10 mg and 2.3 mg/10 mg was obtained for 5-FU and Cel, respectively. By Eudragit S 100 (Ed) coating, significant pH-dependent release profile was achieved, and no drug release was observed in simulated gastric and intestinal fluids. The developed MSs exhibited the release of 92.1±2.9% of 5-FU in 8h whereas 18.9±0.7% Cel was found to be released from the developed MSs. The drug-loaded MSs exhibited appreciable potency against HT-29 cells with an IC50 value of 35.9 μM.
 Conclusion: The results indicated that these microparticles are a promising vehicle for selectively targeting drugs to the colon in the chemotherapy of colon cancer.
Highlights
Colorectal cancer (CRC) is the third leading cause of death in all kinds of cancer after lung and liver cancer followed by stomach and breast cancer [1]
Fourier transform infrared spectroscopy (FTIR) spectrum showed characteristic peak due to pure 5-FU at 1641 and 1229 cm−1 correspond to the C=O and C-X, respectively
The spectrum of EdCH-5-FU-Cel-MSs indicated that characteristic peaks of 5-FU, Cel, and Eudragit S 100 (Ed) are present in the PM of drugs and excipients as well as in the drug-loaded MSs
Summary
Colorectal cancer (CRC) is the third leading cause of death in all kinds of cancer after lung and liver cancer followed by stomach and breast cancer [1]. Despite its efficacy against CRC, 5-FU suffers from several drawbacks including a short biological half-life, invariable oral bioavailability, the requirement of multiple dosages for successful chemotherapy, and gradual increase in the drug resistance [6]. This chemotherapeutic agent is administered as continuous intravenous infusion which causes side effects in nontargeted organs . A study was conducted on the role of Cel in familial adenomatous polyposis (FAP) which shows twice daily dose of 400 mg of Cel significantly reduced the number and size of colorectal polyps [12]. Cel is approved by US Food and Drug Administration in the patients of FAP as add-on therapy to inhibit the growth of adenomatous polyps [13,14]
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