Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA, 02215, USA.
Department of Chemistry, Boston University, 712 Beacon Street, Boston, MA, 02215, USA.
Angew Chem Int Ed Engl. 2020 Jan 7;59(2):704-710. doi: 10.1002/anie.201911720. Epub 2019 Nov 27.
Mucoadhesive polymers are of significant interest to the pharmaceutical, medical device, and cosmetic industries. Polysaccharides possessing charged functional groups, such as chitosan, are known for mucoadhesive properties but suffer from poor chemical definition and solubility, while the chemical synthesis of polysaccharides is challenging with few reported examples of synthetic carbohydrate polymers with engineered-in ionic functionality. We report the design, synthesis, and evaluation of a synthetic, cationic, enantiopure carbohydrate polymer inspired by the structure of chitosan. These water-soluble, cytocompatible polymers are prepared via an anionic ring-opening polymerization of a bicyclic β-lactam sugar monomer. The synthetic method provides control over the site of amine functionalization and the length of the polymer while providing narrow dispersities. These well-defined polymers are mucoadhesive as documented in single-molecule scale (AFM), bulk solution phase (FRAP), and ex vivo tissue experiments. Polymer length and functionality affects bioactivity as long, charged polymers display higher mucoadhesivity than long, neutral polymers or short, charged polymers.
粘弹性聚合物在制药、医疗器械和化妆品行业具有重要的应用价值。具有带电官能团的多糖，如壳聚糖，具有粘弹性，但存在化学定义和溶解度差的问题，而多糖的化学合成具有挑战性，仅有少数具有工程化离子官能团的合成碳水化合物聚合物的报道实例。我们报告了一种受壳聚糖结构启发的合成、阳离子、手性纯碳水化合物聚合物的设计、合成和评价。这些水溶性、细胞相容性聚合物是通过双环β-内酰胺糖单体的阴离子开环聚合制备的。该合成方法可控制胺官能化的位置和聚合物的长度，同时提供较窄的分散度。正如在单分子尺度（AFM）、体相溶液（FRAP）和离体组织实验中所证明的那样，这些聚合物具有粘弹性。聚合物的长度和功能会影响生物活性，因为长的、带电荷的聚合物比长的、中性的聚合物或短的、带电荷的聚合物具有更高的粘弹性。
