Liquid, injectable hydrophobic polymers have advantages as degradable drug delivery vehicles; however, polymers examined for this purpose to date form acidic degradation products that may damage acid-sensitive drugs. Herein, we report on a new viscous liquid vehicle, poly(trimethylene carbonate-co-5-hydroxy-trimethylene carbonate), which degrades through intramolecular cyclization producing glycerol, carbon dioxide, and water-soluble trimethylene carbonate. Copolymer degradation durations from weeks to months were achieved with the 5-hydroxy-trimethylene carbonate (HTMC) content of the oligomer having the greatest impact on the degradation rate, with oligomers possessing a higher HTMC content degrading fastest. The degradation products were non-cytotoxic towards 3T3 fibroblasts and RAW 264.7 macrophages. These copolymers can be injected manually through standard gauge needles and, importantly, during in vitro degradation, the microenvironmental pH within the oligomers remained near neutral. Complete and sustained release of the acid-sensitive protein vascular endothelial growth factor was achieved, with the protein remaining highly bioactive throughout the release period. These copolymers represent a promising formulation for local and sustained release of acid sensitive drugs.

中文翻译：

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液体可降解聚（碳酸三亚甲基酯-co-5-羟基-三亚甲基碳酸酯）：酸敏感性药物的可注射药物递送载体。

液体，可注射的疏水性聚合物具有可降解药物递送载体的优点；但是，迄今为止为此目的而检查的聚合物会形成酸性降解产物，可能会损坏对酸敏感的药物。在此，我们对新的粘性液体的车辆报告，聚（三亚甲基碳酸盐合作-5-羟基-碳酸三亚甲基酯），通过分子内环化作用降解，生成甘油，二氧化碳和水溶性碳酸三亚甲基酯。共聚物的降解持续时间从数周到数月不等，其中低聚物的5-羟基三亚甲基碳酸酯（HTMC）含量对降解速率的影响最大，而HTMC含量较高的低聚物降解最快。降解产物对3T3成纤维细胞和RAW 264.7巨噬细胞无细胞毒性。这些共聚物可以通过标准规格的针头手动注入，重要的是，在体外降解过程中，低聚物中的微环境pH值保持接近中性。实现了酸敏感蛋白血管内皮生长因子的完全和持续释放，蛋白质在整个释放过程中保持高度生物活性。这些共聚物代表了对酸敏感药物的局部和持续释放的有前途的制剂。