Abstract:
Pectin solution gelled with chitosan and calcium ion produced composite particles with a
double layer structure, which may contribute to the undesirable premature and localized
release of the drug. The aim of present study was to formulate pectin-chitosan composite
particles of 5-fluorouracil and selection of most satisfactory formulation by in vitro
evaluation. These multiparticulate systems showing simultaneously specific
biodegradability and pH dependent drug release were prepared based on chitosan, pectin,
and calcium ions. Fourier transform infrared spectroscopic (FTIR) studies and
Differential scanning calorimeter (DSC) studies were performed to study drug and
excipients compatibility. The pectin-chitosan composite particles were prepared by
complex coacervation from chitosan and pectin dispersions. Box Behnken Design was
used to optimize three critical formulation parameters; concentration of chitosan,
pectin and calcium chloride. The pectin-chitosan composite particles were characterized
for particle size, % yield, swelling ratio and percent drug entrapment. Scanning electron
microscopy was performed to study morphological behavior. In vitro drug dissolution
was performed using dissolution apparatus (USP type I). Cytotoxicity study was
performed on HCT-15 colon carcinoma cell line using MTT assay. Stability study was
performed at room temperature and accelerated condition. FTIR and DSC study confirmed that the drug and excipients was found to be compatible. Particle size, %yield,
swelling ratio and percent drug entrapment of optimized batch containing chitosan
0.1%w/w, pectin 10%w/w and calcium chloride 11%w/w were found to be
2.00±0,007mm, 87.57±0.05%, 357±2.45% and 96.77±0.90% respectively. SEM images
of pectin-chitosan composite particles confirmed spherical shape and complexation. In
vitro drug dissolution study confirmed that negligible drug was released from the
chitosan-pectin composite particles in pH 1.2 HCl. Pectin degrading enzyme increased
the protein release from 31.15±0.005 to 92.84±0.007% within 12 h in phosphate buffer
saline pH 7.4 . Cell line toxicity study had confirmed the better anticancer activity of
pectin-chitosan composite particles against human colorectal adenocarcinoma cell line
HCT-15. Hence, the developed 5-fluorouracil containing pectin-chitosan composite
particles were effectively target the colon and shows better anticancer activity in colon
cancer. These characteristics of the chitosan-pectin composite particles would be
promising tool for targeting anticancer drugs to the colon.
