Domb A J, Rock M, Perkin C, Yipchuck G, Broxup B, Villemure J G
Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Biomaterials. 1995 Sep;16(14):1069-72. doi: 10.1016/0142-9612(95)98902-q.
The elimination of a clinically used anticancer biodegradable polymer implant (Gliadel) in the rabbit brain was studied. The implant is composed of N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) (1.6 wt%) dispersed in a copolyanhydride matrix of 1,3-bis(p-carboxyphenoxypropane) (CPP) and sebacic acid (SA) in a 20:80 molar ratio. Four groups of rabbits were implanted with wafers loaded with BCNU, one in a 14C-SA-labelled polymer, another in a 14C-CPP-labelled polymer and two groups with 14C-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the 14C-SA-labelled polymer, approximately 10% of the radioactivity was found in the urine and 2% in the faeces, and about 10% remained in the device 7 d after implantation. In contrast, only 4% of the radioactivity of the 14C-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9 d, and at 21 d, 64% of the implanted 14C-CPP was found in the urine and faeces, and 29% was still in the recovered wafers. Approximately 50% of the BCNU in the wafers was released in 3 d, and over 95% was released after 6 d in the rabbit brain. This study demonstrates that BCNU-loaded polyanhydride is biodegradable and is excreted from the body primarily through the renal system. The water-soluble components SA and BCNU were rapidly excreted, while the insoluble CPP was gradually eliminated after a lag time of 9 d.
研究了一种临床使用的抗癌可生物降解聚合物植入物（Gliadel）在兔脑中的消除情况。该植入物由分散于1,3-双（对羧基苯氧基丙烷）（CPP）和癸二酸（SA）摩尔比为20:80的共聚酸酐基质中的N,N-双（2-氯乙基）-N-亚硝基脲（BCNU）（1.6 wt%）组成。四组兔子被植入载有BCNU的薄片，一组植入14C-SA标记的聚合物，另一组植入14C-CPP标记的聚合物，还有两组植入不含标记物但含14C-BCNU的聚合物，一组用于BCNU处置研究，另一组用于残留药物研究。在植入14C-SA标记聚合物的兔子中，约10%的放射性在尿液中被发现，2%在粪便中，植入后7天约10%仍留在装置中。相比之下，在此期间，14C-CPP标记聚合物的放射性仅4%在尿液和粪便中被发现。然而，9天后发现CPP排泄量急剧增加，在21天时，植入的14C-CPP的64%在尿液和粪便中被发现，29%仍在回收的薄片中。薄片中约50%的BCNU在3天内释放，在兔脑中6天后超过95%被释放。这项研究表明，载有BCNU的聚酸酐是可生物降解的，并且主要通过肾脏系统从体内排出。水溶性成分SA和BCNU迅速排出，而不溶性的CPP在9天的滞后时间后逐渐消除。
