Effect of the Subcutaneous Environment on Phase-Sensitive In Situ-Forming Implant Drug Release, Degradation, and Microstructure.
Effect of the Subcutaneous Environment on Phase-Sensitive In Situ-Forming Implant Drug Release, Degradation, and Microstructure.
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DOI：
10.1002/jps.24673
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发表时间：
2015-12
影响因子：
3.8
通讯作者：
Exner AA
中科院分区：
文献类型：
--
作者：
Solorio L;Exner AA
原位成形植入物是一种很有前途的用于释放治疗剂的平台。当植入物在体内使用时，相对于在体外形成的植入物，会发生显著的行为变化。为了了解注射部位对种植体行为的影响，我们在Sprague Dawley大鼠模型皮下注射聚（乳酸-羟基乙酸）种植体后对其进行了检查，以确定环境如何改变种植体的侵蚀、降解、肿胀、微观结构和模拟药物释放。随着时间的推移，体内形成的种植体微观结构发生了变化，观察到孔隙度在5 d的过程中消失。相对于体外形成的种植体，体内形成的种植体有更大的爆裂释放（p<0.05）。而在释放扩散期，体外种植体的日释放量显著高于体外种植体（2.1%/d, p<0.05），这与种植体微观结构的变化有关。此外，与体内形成的植入物相比，体外形成的植入物一级降解动力学增加了2倍。这些研究结果表明，种植体行为的改变是由外部环境引起的种植体微观结构变化的结果。
In situ forming implants are a promising platform used for the release of therapeutic agents. Significant changes in behavior occur when the implants are used in vivo relative to implants formed in vitro. To understand how the injection site effects implant behavior, poly(lactic-co-glycolic acid) implants were examined after injection in the subcutaneous space of a Sprague Dawley rat model to determine how the environment altered implant erosion, degradation, swelling, microstructure and mock drug release. Changes in implant microstructure occurred over time for implants formed in vivo, where it was observed that the porosity was lost over the course of 5 d. Implants formed in vivo had a significantly greater burst release (p<0.05) relative to implants formed in vitro. However during the diffusion period of release, implants formed in vitro had a significantly higher daily release (2.1%/day, p<0.05), which correlated to changes in implant microstructure. Additionally, implants formed in vitro had a 2 fold increase in the first order degradation kinetics relative to the implants formed in vivo. These findings suggest that the changes in implant behavior occur as a result of changes in the implant microstructure induced by the external environment.