Chitosan microspheres for the specific delivery of amoxycillin to the gastric cavity

Among the different methods for achieving stomach-selective drug delivery t he use of mucoadhesive microspheres holds great promise. The aim of this st udy was to produce polysaccharide chitosan microspheres and investigate the ir potential use for the delivery of antibiotics to the gastric mucous memb rane. Chitosan was chosen because of its mucoadhesive and biodegradable pro perties. In order to design microspheres suitable for stomach-specific drug delivery, it was necessary to address the problem of the high solubility o f this biopolymer in acidic media and consequently, its limited capacity fo r controlling release of the entrapped drug in the stomach cavity. These li mitations were overcome by re-acetylating chitosan upon exposure to acetic anhydride during the microsphere formation process. Using a single-step pro cedure, it was possible to encapsulate hydrophilic antibiotics such as amox icillin (about 100% encapsulation efficiency) and provide different release patterns depending on the type of chitosan used and the extent of re-acety lation. More specifically, polymer solubility and microsphere surface poros ity were adjusted by re-acetylation of the free amino groups, thereby contr olling release of the encapsulated amoxicillin. Fluorescent microspheres we re also obtained using a fluorescent derivative of chitosan, and the intera ction of chitosan microspheres with the gastric mucous membrane was evaluat ed in BALB-c mice following oral administration. Examination of stomach tis sue by florescence microcopy demonstrated that chitosan microspheres could cross the epithelial barrier and were located inside gastric epithelial cel ls at 1 h post-administration. Furthermore, it was observed that the micros pheres remained internalized at 96 h post-administration, suggesting their ability to provide sustained intramucosal delivery of the associated antibi otic. These findings support the potential use of chitosan microspheres in the treatment of gastric diseases caused by Helicobacter pylori.