(9a) Silica-Chitosan Nanocomposite for pH-Responsive, Stomach-Targeted Delivery of Therapeutics

It has already been confirmed that mucoadhesive drug delivery carriers, referred to as the Adhesive Micromatrix System, can adhere to the stomach wall in rats, thereby, remaining longer in the gastrointestinal (GI) tract. In recent years, chitosan and its derivatives have been widely assessed for the controlled release, or the delivery, of various drugs. Besides being biocompatible and biodegradable, chitosan offers advantages in drug delivery because of its permeation enhancement, mucoadhesiveness, and ability for sustained drug release. Illum et. al. reported that chitosan solutions, even at a low concentration (0.5%), are highly effective at increasing the adsorption of insulin across nasal mucosa in rats and sheep. It was suggested that the enhancement mechanism was a combination of bioadhesion and transient widening of the tight junction in a membrane. We intend to develop a chitosan drug delivery system that adheres to stomach mucosurface and delivers antibiotics closer to sites infected by H Pylori. However, due to its high solubility in acid, a composite form of chitosan is needed to prolong the residence and delivery time in stomach. The goal of this project is to develop a composite drug delivery system made by entrapping chitosan polymer with silica network. We demonstrated a process that an in-situ gelation of surface modified silica networks in the presence of chitosan created an interpenetrating network of silica and chitosan macromolecules. Silica gel is very stable in acid. The tight entanglement structure in a silica-chitosan composite could significantly retard chitosan’s leaching under acidic environment. Therefore, in the gastric environment, this composite would control the drug release rate more effectively than bare chitosan. 

In this study, amoxicillin, a small antibiotic drug, was selected to demonstrate the feasibility of using a silica-chitosan nanocomposite as a delivery device in the gastric cavity. The treatment efficacy could be substantially enhanced by the muco-adhesiveness of the silica-chitosan composite. Consequently, the aim of this study was to investigate the effect of the novel chitosan/silica nanocomposite compared with chitosan sponges on the mucosal adsorption of a model drug, amoxicillin, in vitro.