Dual-layered pH-sensitive alginate/chitosan/kappa-carrageenan microbeads for colon-targeted release of 5-fluorouracil.

A new pH-sensitive drug carrier based on alginate (Alg), chitosan (Cs), and kappa-carrageenan (kC) marine biopolymers was developed, comprising a dual-layered polyelectrolyte complexes microbead structure. Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were used to investigate the structures, thermal stability, and morphological changes, respectively, of the microcapsules we developed. In the intestinal environment (pH 7.4), the stability and swelling of Alg microbeads were enhanced after generation of the dual-layered polyelectrolyte complexes. The in vitro release profiles of 5-fluorouracil under simulated GI conditions were also examined. At gastric pH (1.2), the cumulative 5-FU release percentage was decreased by introduction of the additional kC layer from 14% in Alg/Cs microbeads to 7% in the dual-layered Alg/Cs/kC microbeads. Additionally, the release profiles were greatly improved under simulated intestinal and colon conditions. Finally, the microbeads were all biodegradable and showed no cytotoxicity in Chang liver cells. Our results clearly indicate that the dual-layer pH-sensitive Alg/Cs/kC microbeads could be used effectively for the targeted delivery of anticancer drugs to the colon.