Hwang Jungyeon, Li Ronald C, Maynard Heather D
Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA.
J Control Release. 2007 Oct 8;122(3):279-86. doi: 10.1016/j.jconrel.2007.04.010. Epub 2007 Apr 21.
Polymers with reactive side chains and narrow molecular weight distributions were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, and the potential to utilize these polymers to prepare drug carriers was demonstrated. p-Nitrophenyl methacrylate (NPMA) and diethoxypropyl methacrylate (DEPMA) were polymerized utilizing cumyl dithiobenzoate (CDB) as the chain transfer agent and azobisisobutyronitrile (AIBN) as the initiator to high conversions (> or = 86%). The resulting pNPMA and pDEPMA had narrow molecular weight distributions (polydispersity indices < 1.3). The ability to functionalize these polymers was confirmed. For pNPMA, up to 86% of the side chains were substituted with the amino acid, glycine methyl ester. The side chains of pDEPMA were hydrolyzed to aldehydes and reaction with O-benzylhydroxylamine and O-methylhydroxylamine to form stable oxime bond conjugates was demonstrated. The percent substitution depended on the feed ratios. Conjugation of an aminooxy-functionalized RGD peptide was also demonstrated.
通过可逆加成-断裂链转移（RAFT）聚合反应合成了具有反应性侧链且分子量分布窄的聚合物，并证明了利用这些聚合物制备药物载体的潜力。以二硫代苯甲酸枯基酯（CDB）为链转移剂、偶氮二异丁腈（AIBN）为引发剂，将对硝基苯基甲基丙烯酸酯（NPMA）和二乙氧基丙基甲基丙烯酸酯（DEPMA）聚合至高转化率（≥86%）。所得的聚对硝基苯基甲基丙烯酸酯（pNPMA）和聚二乙氧基丙基甲基丙烯酸酯（pDEPMA）具有窄的分子量分布（多分散指数<1.3）。证实了这些聚合物功能化的能力。对于pNPMA，高达86%的侧链被氨基酸甘氨酸甲酯取代。pDEPMA的侧链被水解为醛，并证明了其与O-苄基羟胺和O-甲基羟胺反应形成稳定的肟键共轭物。取代百分比取决于进料比。还证明了氨基氧基功能化的RGD肽的共轭。
