Microcapsules combining alginate, chitosan, poly-l-lysine and polyethyelene glycol for liver cell transplant and cell therapy applications

Liver diseases are the eighth leading cause of death in North America. Currently, liver transplant is the available treatment for patients with liver failure. However, the shortage of donors and the requirement of immunosuppressant remain a disadvantage. Microencapsulation of living cells is an emerging technology which may serve as an alternative therapy for patients requiring organ transplants. One of the limiting factors in the progress of such therapy is attaining a biocompatible and mechanically stable polymer. In the following thesis, a novel microcapsules combining alginate, poly-l-lysine, chitosan and polyethylene glycol (ACPPA) was designed and evaluated for its use in the treatment of liver failure. In vitro studies were also conducted to compare the novel membrane, with other microcapsules, including the widely studied APA microcapsules as well as alginate coated with chitosan (AC), APA with PEG (APPA) and AC with PEG (ACP). Results show that the novel membrane can support liver cell proliferation and function and is capable of providing cell immuno-protection. The study reveals that chitosan and PEG containing microcapsules can be an alternate material for cell microencapsulation to be used for live cell delivery and other biomedical applications. Further in-vivo studies are recommended to evaluate the full potentials

Novel multi-layer APPPA microcapsules for oral delivery: preparation condition, stability and permeability

491-497Oral therapy utilizing cell microencapsulation has shown promise in the treatment of many diseases. Current obtainable microcapsule membranes, however, show inadequate stability in the gastrointestinal (GI) environment, thus restricting the general application of live cells for oral therapy. To overcome this limitation, we have previously developed a novel multi-layer alginate/poly-L-lysine/pectin/poly-L-lysine/alginate microcapsule (APPPA) with demonstrated improvement on membrane stability over the frequently reported alginate/poly-L-lysine/alginate (APA) microcapsules. In this study, we further examined the effects of preparation conditions on microcapsule formation, and assessed the membrane strength and GI stability. Results showed that increased membrane strength of the APPPA microcapsules was attained by using pectin with low degree of esterification as the mid-layer material, saline as the solvent for the preparation solutions and washing medium, and 0.1 M CaCl2 as the gelling solution for alginate cores. Resistance of this membrane to the simulated GI fluids was also investigated. Permeability of and release profiles from the APPPA microcapsules were found comparable to the APA microcapsules. These findings suggested that the multi-layer APPPA microcapsule formulation may have potential in oral delivery of proteins, live bacterial cells and other biomedical applications