Dang W, Daviau T, Brem H
Guilford Pharmaceuticals, Inc., Baltimore, Maryland 21224, USA.
Pharm Res. 1996 May;13(5):683-91. doi: 10.1023/a:1016035229961.
The objectives of the current study are to characterize the distribution of the chemotherapeutic agent carmustine (BCNU) in spray dried polyanhydride microspheres and to describe the morphological changes that occur during the in vitro and in vivo erosion of the polyanhydride implant--GLIADEL, which consists of BCNU distributed in the copolymer matrix of poly(carboxyphenoxy propane:sebacic acid) in a 20:80 molar ratio (p(CPP:SA, 20:80)).
Scanning electron microscopy (SEM) was used to visualize the morphological changes of the polymer during the manufacturing process and in vitro and in vivo erosion.
This study revealed that BCNU was homogeneously distributed within spray dried polyanhydride microspheres with no phase separation. The porosity of the wafer fabricated from spray dried polyanhydride microspheres gradually increased during erosion. During the initial period following wafer implantation in the brains of rats, erosion was mainly confined to the surface layer of the wafer with the majority of the wafer remaining intact. The eroding front gradually advanced from the surface to the interior of the wafer in a layerwise fashion, creating pores and connecting channel. Eventually both the interior and exterior of the wafers were eroded and the same porous structure was seen throughout the whole wafer.
This study provides the first visual observation of the morphological changes of the GLIADEL(R) wafer during erosion of the polyanhydride matrix and release of the drug substance BCNU. The observations in this study support the conclusion that BCNU release from a polyanhydride wafer is controlled both by diffusion of the drug and erosion of the polymer matrix.
本研究的目的是表征化疗药物卡莫司汀（BCNU）在喷雾干燥的聚酸酐微球中的分布，并描述聚酸酐植入物——Gliadel在体外和体内侵蚀过程中发生的形态变化。Gliadel由以20:80摩尔比分布在聚（羧苯氧基丙烷：癸二酸）共聚物基质（p（CPP:SA，20:80））中的BCNU组成。
使用扫描电子显微镜（SEM）观察聚合物在制造过程以及体外和体内侵蚀过程中的形态变化。
本研究表明，BCNU均匀分布在喷雾干燥的聚酸酐微球内，无相分离现象。由喷雾干燥的聚酸酐微球制成的薄片在侵蚀过程中孔隙率逐渐增加。在薄片植入大鼠脑内后的初始阶段，侵蚀主要局限于薄片的表层，薄片的大部分保持完整。侵蚀前沿以分层方式从薄片表面逐渐向内部推进，形成孔隙和连通通道。最终，薄片的内部和外部都被侵蚀，整个薄片呈现相同的多孔结构。
本研究首次直观观察了Gliadel薄片在聚酸酐基质侵蚀和药物BCNU释放过程中的形态变化。本研究中的观察结果支持以下结论：聚酸酐薄片中BCNU的释放受药物扩散和聚合物基质侵蚀的共同控制。
