In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams
In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams
复制标题
DOI：
10.1016/s0142-9612(00)00047-8
复制
发表时间：
2000-09-01
期刊：
影响因子：
14
通讯作者：
Mikos, AG
中科院分区：
文献类型：
--
作者：
Lu, L;Peter, SJ;Mikos, AG
本研究研究了聚乳酸-乙醇酸共聚物(PLGA)多孔泡沫在37℃、pH 7.4的磷酸盐缓冲盐水(PBS)中20周内的体外降解，以及植入大鼠肠系膜8周后的体内降解。采用溶剂浇注、颗粒浸出法制备了三种PLGA 85：15和三种50：50泡沫塑料。这两种类型的初始盐质量分数分别为80%和90%，盐粒大小为106-150微米，而第三种类型的初始盐质量分数为90%，粒度范围为0-53微米，制得的PLGA 85：15泡沫的孔隙率分别为0.82、0.89和0.85，PLGA 50：50泡沫的孔隙率分别为0.73、0.87和0.84。相应的中位孔径PLGA 85：15为30、50和17微米，PLGA 50：50为19、17和17微米。PLGA 85：15泡沫塑料的体内外降解动力学与孔形态无关，在降解过程中泡沫塑料的重量、厚度、孔分布、压缩蠕变行为和形态变化不大。以重均相对分子质量为基础的体外泡沫半衰期分别为11.1+/-1.8(80%，106-150微米)、12.0+/-2.0(90%，106-150微米)和11.6+/-1.3(90%，0-53微米)周，与体内降解的相应数值9.4+/-2.2、14.3+/-1.5和13.7+/-3.3周相似。相比之下，所有人都是PLGA 50。50个泡沫在与PBS孵育6-8周后，泡沫重量、吸水率和孔分布都发生了显著变化。体外泡沫半衰期分别为3.3+/-0.3(80%，106-150微米)、3.0+/-0.3(90%，106-150微米)和3.2+/-0.1(90%，0-53微米)周，体内半衰期分别为1.9+/-0.1周、2.2+/-0.2周和2.4+/-0.2周。与85：15泡沫相比，PLGA 50：50的半衰期明显缩短，这表明它们在体外和体内的降解速度都更快。此外，由于植入物周围介质中累积的酸性降解产物的自催化作用，PLGA 50：50泡沫在体内的降解速度明显快于体外条件。这些结果表明，聚合物组成和环境条件对多孔PLGA泡沫塑料的降解速度有显著影响。(C)2000爱思唯尔科学有限公司。保留所有权利。
This study investigated the in vitro degradation of porous poly(DL-lactic-co-glycolic acid) (PLGA) foams during a 20-week period in pH 7.4 phosphate-buffered saline (PBS) at 37 degrees C and their in vivo degradation following implantation in rat mesentery for up to 8 weeks. Three types of PLGA 85 : 15 and three types of 50 : 50 foams were fabricated using a solvent-casting, particulate-leaching technique. The two types had initial salt weight fraction of 80 and 90%, and a salt particle size of 106-150 mu m, while the third type had 90% initial weight fraction of salt in the size range 0-53 mu m. The porosities of the resulting foams were 0.82, 0.89, and 0.85 for PLGA 85:15, and 0.73, 0.87, and 0.84 for PLGA 50:50 foams, respectively. The corresponding median pore diameters were 30, 50, and 17 mu m for PLGA 85 : 15, and 19, 17, and 17 mu m for PLGA 50 : 50. The in vitro and in vivo degradation kinetics of PLGA 85 : 15 foams were independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. The in vitro foam half-lives based on the weight average molecular weight were 11.1 +/- 1.8 (80%, 106-150 mu m), 12.0 +/- 2.0 (90%, 106-150 mu m), and 11.6 +/- 1.3 (90%, 0-53 mu m) weeks, similar to the corresponding values of 9.4 +/- 2.2, 14.3 +/- 1.5, and 13.7 +/- 3.3 weeks for in vivo degradation. In contrast, all PLGA 50. 50 foams exhibited significant change in foam weight, water absorption, and pore distribution after 6-8 weeks of incubation with PBS. The in vitro foam half-lives were 3.3 +/- 0.3 (80%, 106-150 mu m), 3.0 +/- 0.3 (90%, 106-150 Irm), and 3.2 +/- 0.1 (90%, 0-53 mu m) weeks, and the corresponding in vivo half-lives were 1.9 +/- 0.1, 2.2 +/- 0.2, and 2.4 +/- 0.2 weeks. The significantly shorter half-lives of PLGA 50 : 50 compared to 85 : 15 foams indicated their faster degradation both in vitro and in vivo. In addition, PLGA 50 : 50 foams exhibited significantly faster degradation in vivo as compared to in vitro conditions due to an autocatalytic effect of the accumulated acidic degradation products in the medium surrounding the implants. These results suggest that the polymer composition and environmental conditions have significant effects on the degradation rate of porous PLGA foams. (C) 2000 Elsevier Science Ltd. All rights reserved.