Artificial cell microcapsules for oral delivery of thalidomide for use in Crohn's disease: Design, preparation, and in-vitro analysis

A delivery method for the oral administration of thalidomide for lowering tumor necrosis factor alpha (TNT-alpha), and thus Crohn's disease-related inflammation in the proximal small intestine, using two separate engineered polymer microcapsules is explored in this thesis. Membrane formation of both alginate-polylysine-alginate (APA) and alginate-chitosan (AC) capsules are discussed and thalidomide encapsulation procedures have been described. In-vitro tests have been used to monitor capsule degradation and drug release in a simulated gastrointestinal environment. Also, culture and use of RAW 264.7 mouse macrophage cells for the simulation of the human intestine is described. Results show two separate methods of drug delivery by the APA and AC capsules. APA capsules release thalidomide in a timed-release fashion whereas AC capsules release the drug in a burst manner. These results implicate the benefits of the use of both capsules to target separate sites along the small intestine. Also the cultured macrophage studies conclude that the proposed encapsulation therapy does indeed lower TNF-alpha levels and could therefore be of benefit for the lowering of inflammation associated with Crohn's disease. However, further animal study is needed before full potential of this approach can be realized.