Application of Chitosan-Based Gels in Pharmaceuticals - Chitosan Based Hydrogels: Functions and Applications - page 324

[62]. However, the high aqueous solubility of chitosan restricts the utility of CMs for gastric
drug delivery. Reacetylated chitosan microspheres were prepared with suitable properties
for the controlled release of amoxicillin and metronidazole in the gastric cavity and, hence,
for the eradication of H. pylori in gastric ulcers and possibly gastric carcinoma [63].
7.4.2.2 Colon-Selective Drug Delivery
The colon is a site for the administration of protein and peptides that are degraded by
digestive enzymes in the upper GI tract. The absorption of peptide and protein drugs
could be enhanced in the colon because of the low activity of proteolytic enzymes there
and the long residence time. In addition, it is more effective in treating colonic diseases
such as ulcerative colitis, colorectal cancer, and Crohn's disease with direct delivery of
drugs to the affected area [64].
Chitosan is a promising polymer for colon drug delivery since it can be biodegraded by
the colonic bacterial flora and is toxicologically harmless with low cost. As a result, this
compound could be promising for colon-specific drug delivery [65].
Hydroxypropyl methylcellulose phthalate, an enteric-coating material, was used to coat
chitosan capsules loaded with insulin [66]. At 2 h after oral administration, the capsules
were eliminated from the stomach. After 2-6 h, the capsules moved into the small intestine
and were in the large intestine after 6-12 h. For in vitro release medium, cecal content from
rats was suspended in two volumes of bicarbonate buffer and the pH was adjusted to 7.0.
The release of 5(6)-carboxyfluorescein loaded in chitosan capsules, a model water-soluble
compound, was increased in the rat cecal content suspension as compared to simulated
gastric juice (pH 1.2) and simulated intestinal juice (pH 6.8). While the entire drug was
released after 12 h in the cecal suspension, only 20% was released in the simulated intesti-
nal juice after 6 h, and none was released in the simulated gastric juice after 2 h. Degradation
of chitosan capsules in cecal contents facilitated the release of 5(6)-carboxyfluorescein.
Tominaga et al. [67] prepared a colon-targeted formulation by using a double coating
system. The core, composed of acetaminophen, was coated with an inner coating layer
made of chitosan and an outer coating layer made of phytin, a gastric acid-resistant mate-
rial. While the outer layer protected the core from acidic conditions in the stomach and
was then dissolved in the small intestine, the inner layer protected the core in the small
intestine and was then biodegraded in the colon where the drug was released.
5-Aminosalicylic acid, a cyclooxygenase inhibitor and an antiinflammatory drug effec-
tive against Crohn's disease and ulcerative colitis, is rapidly absorbed from the small intes-
tine. Eudragit-coated chitosans (200 μm) have been developed by an emulsion-solvent
evaporation technique based on a multiple water/oil/water emulsion to deliver it specifi-
cally to the colon [68].
Albendazole was delivered specifically into the colon by microspheres of chitosan hydro-
chloride, and drug release in 24 h was 48.9% and 76.5% in colonic fluid without and with
rat cecal contents, respectively [69].
Sadeghi et al. [70] synthesized the TMC- and diethylmethyl-chitosan nanoparticles
loaded with insulin by the polyethylcyanoacrylate (PEC) technique and the ionic gelation
technique, and the results showed that nanoparticles prepared by the PEC method had a
higher insulin loading efficiency and zeta potential than those prepared by the ionotropic
gelation method . The PEC method of nanoparticle preparation gave particles in the range
of 170-270 nm with spherical and smooth surface morphology and the polydispersity
index (PDI) below 0.3. In vitro release studies showed a small burst effect at the beginning
and then a sustained release characteristic for 5 h. Ex vivo investigations revealed better