Preparation and characterization of crosslinked chitosan microspheres for the colonic delivery of 5‐fluorouracil

Abstract

In this work, we attempted to develop a simple and inexpensive colon specific pulsatile drug‐delivery system using chitosan microspheres loaded with 5‐fluorouracil (5‐FU) using an enteric‐coated soft gelatin capsule. Chemical crosslinking by glutaraldehyde and interactions between the polymer and the drug were determined by Fourier transform infrared spectral study. Scanning electron microscopy of the microspheres revealed spherical shapes with smooth surfaces. Differential scanning calorimetry studies confirmed the molecular dispersion of the drug in the polymer matrix. Three different formulations (i.e., F1, F2, and F3) were prepared by the variation of the amount of 5‐FU. Encapsulation efficiencies of 5.5, 10.8, and 17.9% for drug loadings of 10, 20, and 50%, respectively, were obtained. In vitro release studies were conducted at pH 1.2 and pH 7.4 (to simulate actual gastrointestinal fluid and gastrointestinal tract conditions, respectively). The results indicate that chitosan microspheres released 5‐FU in both acidic (60%) and basic pH (40%) conditions, whereas the capsule (filled with chitosan microspheres) showed only 8–10% release in acidic media and nearly 90% in basic media within 12 h. The newly designed pulsatile capsule device could be used for targeting 5‐FU to the colon. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Loading and release of 5-fluorouracil from HY zeolites with varying SiO2/Al2O3 ratios

“…In order to elucidate the role of aluminum in the loading and release of 5-FU in zeolite Y, 27 Al MAS NMR spectra were acquired for HY parent and 5-FU loaded samples (Fig. 6).…”

“…27 Al Magic Angle Spinning (MAS) NMR experiments were conducted on both 5-fluorouracil loaded and parent HY zeolite samples. AlCl 3 was used as a chemical shift reference for 27 Al NMR. The spinning speed for all 27 Al experiments was 30 kHz.…”

“…AlCl 3 was used as a chemical shift reference for 27 Al NMR. The spinning speed for all 27 Al experiments was 30 kHz.…”

“…However, the degradation of 5-FU before it reaches the cancerous areas, low 5-FU retention in tumors, drug resistance and toxicity are all problems that limit the clinical use of 5-FU in cancer treatment. Recently, controlled release applications of 5-FU with chitosan complexes [27,28], clays [29,30], zeolitic imidazolate frameworks (ZIFs) [31] and polymer nanoparticles [32] have been reported in the literature.…”

The design of pH-sensitive chitosan-based formulations for gastrointestinal delivery

“…For oral administration of chitosan-based formulations, it is the simplest approach to protect the encapsulated chitosan-based core from the aggressive environments of the stomach. For years, several enteric coating polymers such as polymethacrylates (Eudragit 1 products), cellulose acetate phthalate and cellulose acetate have been applied to coat chitosan-based formulations for intestinal pH-sensitive drug delivery [55][56][57]. Overall, these polymers can maintain rigid status when passing through the stomach, whereas they become soluble at the higher intestine pH and release the drug core ready for action.…”