Polymers, Encapsulation, and Artifical Organs (Report on Session 26.0)

The session "Polymers, Encapsulation, and Artificial Organs" at the Fourth International Symposium on Neurotransplantation consisted of five presentations examining the possibility that polymer capsules with or without cells could have therapeutic application for various neurological diseases. Dr. Robert Langer of the Massachusetts Institute of Technology provided an introduction to the use of polymers as systems for controlled release, long-term drug delivery/4/. Some of these systems are currently in use for the treatment of ophthalmic diseases, tobacco addiction, and birth control, and can continuously release drugs for over one year. Of interest is the use of these slow releasing polymers for delivering drugs and chemicals directly into the brain, bypassing the blood-brain barrier. Polyanhydride-containing bio-erodible polymers were discussed as a way to introduce both large and small molecules into the brain. Dr. Langer suggested that polymers which release drugs by surface erosion, thereby leading to nearly constant release rates, may be the most appropriate delivery system for CNS applications. The polymers are now used clinically in over 56 medical centers in an FDA-approved study examining delivery of BCNU in post-operative patients with primary cerebral malignancy. These polyanhydride polymer wafers are placed in the resection cavity and provide a sustained release of the chemotherapeutic agent. Dr. Langer reported preliminary data demonstrating increased efficacy of the localized BCNU polymer implants over intravenous systemic administration/4/. In another possible application it was shown that polymers impregnated with dopamine could release the compound steadily for over a year. Studies examining dopamine releasing polymers in Parkinson’s disease models are currently underway in several laboratories. Dr. Patrick Aebischer from Brown University presented an overview of data showing the use of polymer membranes to encapsulate cells for transplantation into the nervous system/1/. While the previous presentation described polymers impregnated with dopamine for transplantation into parkinsonian brains, Dr. Aebischer described data demonstrating that dopamine secreting cells can be encapsulated by thermoplastic polymer membranes and virtually made into a living dopamine minipump. These polymer membranes with maximum molecular porosity at about 50,000 MW impair host rejection via either antibody or cellular responses. This allows the use of xenogeneic or allogeneic transplants without the need for pharmacological immunosuppression. The subsequent presentation by Dr. Meg Palmatier from CytoTherapeutics, Inc. gave further details of the basic science and potential clinical application of these encapsulated dopamine implants for Parkinson’s disease/2/. The commercial utilization of these implants involves the use of PC12 cells in PAN/PVC membranes which will be implanted directly into the striata of Parkinson’s disease animal models and humans. These implants were shown to release dopamine continuously and to improve behavioral recovery in rodent and primate models. This product was noted to be undergoing safety and toxicology studies in preparation for commercial marketing. Of interest were additional data which demonstrated that implanting these dopamine sources into aged rodents seemed to improve some of the abnormal motor behavior seen in aged animals.