Comparison of flow and batch polymerization processes for production of vinyl ether terpolymers for use in the delivery of siRNA. Issue 8 (5th February 2014)

• Record Type: Journal Article
• Authors: Nyrop, Jason L.; Soheili, Arash; Xiang, Rong; Meng, Fanyu; Waldman, Jacob H.; Jia, Xiujuan; Parmar, Rubina Giarre; Thuronyi, Benjamin W.; Williams, J. Michael; DiMichele, Lisa; Journet, Michel; Howell, Bonnie J.; Mao, Bing; Davies, Ian W.; Colletti, Steven L.; Sepp‐Lorenzino, Laura; Guidry, Erin N.
• Is Part Of: Journal of polymer science. Volume 52:Issue 8(2014:Apr.)
• Page Start: 1119
• Page End: 1129
• Publication Date: 2014-02-05
• Subjects: amphiphilies -- biological applications of polymers -- cationic polymerization -- copolymerization -- drug delivery systems -- poly(vinyl ethers); 547
• DOI: 10.1002/pola.27094
• Languages: English
• ISSNs: 0887-624X

Abstract

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 BF3 OEt2 ‐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 Abstract : The ability to control the character of the polymer structure in terms of size and monomer incorporation is critical for polymeric biomaterials to move into the clinic. Two scaleable and reproducible processes to prepare amphiphilic terpolymers through a cationic polymerization for use in siRNA delivery are reported. The polymer‐siRNA conjugates derived from polymers produced using these two methods are characterized in vivo, illustrating that control over the method of polymer synthesis can affect the polymer produced.