The approach of this NCDDG is to continue to develop biodegradable polymers that can be implanted at the site of the tumor and release effective drugs in a controlled manner as the polymer is degraded. Other programs are concerned with research related to providing new polymers and delivery systems for anti cancer drugs. Our program is aimed at development and is designed to provide polymer-drug combinations in optimal, reproducible formulations so that they can be tested in animals (preclinical); the effective formulations will be then scaled-up and extensively studied to be appropriate for human clinical trials (beyond the scope of this proposal). Through the previous NCDDG we have established the requirements for a suitable degradable implant to the brain by using the BCNU-polymer combination as representative. During the course of bringing this device through clinical trials many chemical, pharmaceutical, and pharmacological issues were investigated and the appropriate procedures have been established. These include: scale-up and quality control procedures for polymer manufacturing and drug incorporation; toxicology of the placebo and BCNU-loaded polymer under various conditions; and new polymers and various drugs were introduced to the program.
The specific aims of the current proposals are to 1) develop procedures for large scale production of clinical grade drug-polymer implants, focusing on the use of automated compression and injection molding processes, 2) develop methods to produce sufficient quantities of the new polymers and delivery systems developed,in other programs and supply of quality polymers and drug incorporated devices to the other programs, 3) Develop validated methods for the evaluation of the shelf life stability of anticancer polyanhydride delivery systems, 4) develop methods for studying Polymer-Drug interaction and protein stability in polymers, and 5) Determine the optimal gamma- irradiation sterilization dose for polyanhydride based delivery systems.
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