Comparison of flow and batch polymerization processes for production of vinyl ether terpolymers for use in the delivery of siRNA |
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Authors: | Jason L. Nyrop Arash Soheili Rong Xiang Fanyu Meng Jacob H. Waldman Xiujuan Jia Rubina Giarre Parmar Benjamin W. Thuronyi J. Michael Williams Lisa DiMichele Michel Journet Bonnie J. Howell Bing Mao Ian W. Davies Steven L. Colletti Laura Sepp‐Lorenzino Erin N. Guidry |
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Affiliation: | 1. Department of Chemical Engineering, Merck & Co., Inc., , Rahway, New Jersey, 07065;2. Department of Process Chemistry, Merck & Co., Inc., , Rahway, New Jersey, 07065;3. Department of Analytical Chemistry, Merck & Co., Inc., , Rahway, New Jersey, 07065;4. Department of Medicinal Chemistry, Merck & Co., Inc., , West Point, Pennsylvania, 19486;5. Department of RNA Biology, Merck & Co., Inc., , West Point, Pennsylvania, 19486 |
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Abstract: | Synthetic polymers represent a modifiable class of materials that can serve as adjuvants to address challenges in numerous biomedical and medicinal chemistry applications including the delivery of siRNA. Polymer‐based therapeutics offer unique challenges in both synthesis and characterization as compared to small molecule therapeutics. The ability to control the structure of the polymer is critical in creating a therapeutic. Reported herein, are batch and flow polymerization processes to produce amphiphilic terpolymers through a Lewis acid BF3OEt2‐catalyzed polymerization. These processes focus on controlling reaction variables, which affect polymer structure in this rapid, exothermic, nonliving cationic polymerization. In addition to analytical characterization of the polymers, the in vivo activity of the polymer‐siRNA conjugates is also highlighted—demonstrating that the method of synthesis does affect the in vivo activity of the resulting polymer conjugate. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1119–1129 |
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Keywords: | amphiphilies biological applications of polymers cationic polymerization copolymerization drug delivery systems poly(vinyl ethers) |
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