Department of Chemical Engineering, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Human Mobility Research Centre, Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada.
ACS Appl Bio Mater. 2021 Apr 19;4(4):3686-3696. doi: 10.1021/acsabm.1c00160. Epub 2021 Mar 30.
A recently developed viscous liquid aliphatic polycarbonate, poly(trimethylene carbonate--5-hydroxy trimethylene carbonate), has advantageous properties for the delivery of acid-sensitive drugs such as proteins and peptides. This copolymer degrades in vitro via an alkaline-catalyzed intramolecular cyclization reaction yielding oligo (trimethylene carbonate), glycerol, and carbon dioxide, but its in vivo degradation mechanisms are presently unknown. The in vivo degradation mechanism and tissue response to this copolymer were investigated following subcutaneous implantation in Wistar rats. The molecular weight and composition of the copolymer varied in the same manner following subcutaneous implantation as observed in vitro. These findings suggest that the copolymer also degraded in vivo principally via intramolecular cyclization. The tissue response in terms of the inflammatory zone cell density, fibrous capsule thickness, and macrophage response was intermediate to that of two clinically used biodegradable sutures, Vicryl and Monocryl, indicating that the copolymer can be considered biotolerable. Collectively, the data show that further development of this copolymer as a drug delivery material is warranted.
一种最近开发的粘性液体脂肪族聚碳酸酯，聚（三亚甲基碳酸酯-5-羟三亚甲基碳酸酯），具有用于输送酸敏感药物如蛋白质和肽的有利性质。该共聚物通过碱性催化的分子内环化反应在体外降解，生成低聚物（三亚甲基碳酸酯）、甘油和二氧化碳，但目前尚不清楚其体内降解机制。在 Wistar 大鼠皮下植入后，研究了该共聚物的体内降解机制和组织反应。与体外观察到的情况一样，皮下植入后共聚物的分子量和组成也以相同的方式变化。这些发现表明共聚物也主要通过分子内环化在体内降解。就炎症区细胞密度、纤维囊厚度和巨噬细胞反应而言，组织反应处于两种临床使用的可生物降解缝线 Vicryl 和 Monocryl 之间，表明共聚物可以被认为是生物相容的。总的来说，这些数据表明有必要进一步开发这种共聚物作为药物输送材料。
