A novel polyethylene depot device for the study of PLGA and P(FASA) microspheres in vitro and in vivo.
A novel polyethylene depot device for the study of PLGA and P(FASA) microspheres in vitro and in vivo.
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DOI：
10.1016/s0142-9612(02)00183-7
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发表时间：
2002-11
期刊：
影响因子：
14
通讯作者：
M. Sandor;Joshua Harris;E. Mathiowitz
中科院分区：
文献类型：
--
作者：
M. Sandor;Joshua Harris;E. Mathiowitz
聚合物微球（0.5-5.0μm）难以在体内表征，因为它们会降解、迁移和内吞。含有微球的新型聚乙烯网状袋允许从大鼠中回收降解的聚合物产物，而不影响降解速率。将含有聚（乳酸-羟基乙酸）（PLGA）或聚（二十二烷酸-癸二酸）（P（FASA））微球的小袋肌内、皮下和腹膜内植入，并在3、7、14和28天后进行分析。在体内，皮下或腹膜内植入物经历了立即的质量损失和延迟的分子量（Mw）降低。肌内植入物的表现与体外样品相似，Mw立即降低，质量损失滞后。这些结果表明，通常取决于体外分子量损失的质量损失可能直接归因于皮下和腹膜内的酶促降解，而不是水解降解，而肌内植入物似乎主要依赖于水解裂解。这一观察结果得到了组织学的进一步支持。对装载有包封骨保护素（一种用于防止骨吸收的蛋白质药物）的PLGA微球的袋进行的其他实验表明，使用该装置防止了释放研究期间微球离心固有的人为聚合物压缩，并允许从体内植入3天的微球中提取活性蛋白。
Polymer microspheres (0.5–5.0μm) are difficult to characterize in vivo because they degrade, migrate, and are endocytosed. A novel polyethylene mesh pouch containing microspheres allowed for retrieval of degraded polymeric products from rats without affecting the rate of degradation. Pouches containing poly(lactic-co-glycolic acid) (PLGA) or poly(fumaric-co-sebacic acid) (P(FASA)) microspheres were implanted intramuscularly, subcutaneously, and intraperitoneally and analyzed after 3, 7, 14, and 28 days. In vivo, subcutaneous or intraperitoneal implants experienced an immediate mass loss and a delayed decrease in molecular weight (Mw). Intramuscular implants behaved similarly to in vitro samples, decreasing in Mw immediately and lagging in mass loss. These results suggest that mass loss, which is usually dependent on Mw loss in vitro, may be directly due to enzymatic, rather than hydrolytic, degradation subcutaneously and intraperitoneally, while intramuscular implants appear to be mostly dependent on hydrolytic cleavage. This observation is further supported by histology. Additional experiments on pouches loaded with PLGA microspheres encapsulating osteoprotegerin, a protein drug used to prevent bone resorption, revealed that use of the device prevented the artifactual polymer compression inherent to microsphere centrifugation during release studies and allowed for the extraction of active protein from microspheres implanted for 3 days in vivo.