Department of Chemical Engineering, Queen's University, Kingston, Ontario, Canada.
Eur J Pharm Biopharm. 2010 Feb;74(2):172-83. doi: 10.1016/j.ejpb.2009.11.012. Epub 2009 Dec 3.
The potential of osmotic pressure driven release of proteins from poly(trimethylene carbonate) and poly(trimethylene carbonate-co-d,l-lactide) (poly(TMC-co-DLLA)) elastomers with varying amounts of DLLA was investigated using bovine serum albumin (BSA) as a model protein. The BSA was co-lyophilized with either trehalose or trehalose combined with NaCl as osmotigens to produce particles with sufficient osmotic activity. Elastomers composed solely of TMC were not suitable for osmotically driven release when trehalose was the main osmotigen in the solid particles. Copolymerizing TMC with small amounts of DLLA decreased the tear resistance of the elastomer and consequently increased the rate and the total amount of BSA released. Elongation at break played a significant role in determining the osmotic release behavior; elastomers with comparable Young's modulus and tensile strength, but smaller elongation at break, provided faster release rates. Elastomer degradation played a minor role in the osmotic release, as the mechanical properties underwent very little change during the investigated period of release. The poly(TMC-co-DLLA)(80:20) elastomer was able to provide near zero order release of BSA for up to 12days, and the total amount of BSA released was 74+/-4% after 34days, when small amounts of NaCl was added to trehalose. No significant reduction in the microenvironmental pH occurred after 17days of release. TMC elastomers copolymerized with small amounts of DLLA are potential candidates for the localized delivery of acid-sensitive proteins.
研究了不同含量丙交酯（DLLA）的聚三亚甲基碳酸酯（PTMC）和聚三亚甲基碳酸酯-共-D,L-丙交酯（PTMC-co-DLLA）弹性体通过渗透压驱动释放蛋白质的潜力，以牛血清白蛋白（BSA）为模型蛋白。将 BSA 与海藻糖或海藻糖与 NaCl 联合作为渗透压剂共冻干，以产生具有足够渗透压活性的颗粒。当海藻糖是固体颗粒中的主要渗透压剂时，仅由 TMC 组成的弹性体不适合渗透压驱动释放。共聚少量 DLLA 会降低弹性体的撕裂强度，从而提高 BSA 的释放速率和总量。断裂伸长率在确定渗透压释放行为方面起着重要作用；具有可比的杨氏模量和拉伸强度、但断裂伸长率较小的弹性体提供了更快的释放速率。弹性体降解在渗透压释放中作用较小，因为在释放研究期间，力学性能几乎没有变化。当在海藻糖中添加少量 NaCl 时，聚（PTMC-co-DLLA）（80:20）弹性体能够提供长达 12 天的接近零级 BSA 释放，并且在 34 天后，BSA 的总释放量为 74±4%。释放 17 天后，微环境 pH 值没有明显下降。共聚少量 DLLA 的 TMC 弹性体可能是局部递送酸敏感蛋白的候选材料。
