BIODEGRADABLE POLYMERS FOR CONTROLLED DELIVERY OF CHEMOTHERAPY WITH AND WITHOUT RADIATION-THERAPY IN THE MONKEY BRAIN
BIODEGRADABLE POLYMERS FOR CONTROLLED DELIVERY OF CHEMOTHERAPY WITH AND WITHOUT RADIATION-THERAPY IN THE MONKEY BRAIN
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DOI：
10.3171/jns.1994.80.2.0283
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发表时间：
1994-02-01
影响因子：
4.1
通讯作者：
EPSTEIN, JI
中科院分区：
文献类型：
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作者：
BREM, H;TAMARGO, RJ;EPSTEIN, JI
通过可生物降解的聚合物装置持续给药，可以在较长时间内产生高局部组织浓度，从而提高药物的治疗效果。已有研究表明，与全身给药的类似大鼠相比，植入亚硝酸卡莫司汀(BCNU)的控释聚合物可延长9L胶质瘤大鼠的生存期。本研究评价了生物可降解共聚物聚[双(对羧基苯氧基)丙烷]酸酐(PCPP)和癸二酸(SA)以20：80的比例(PCPP：SA)在猴脑组织内给药对BCNU的影响。并评价间质BCNU联合放射治疗的效果。18只雄性食蟹猴随机分为4组：对照组，植入空聚合物组，植入BCNU聚合物组，右脑植入空聚合物，左半球植入BCNU聚合物，然后照射。在特定的时间进行放射学和组织学的疗效评估。发现了大脑对聚合物的局部反应，当聚合物含有BCNU时，这种反应更强烈。术后第14天行放射学检查，观察局部脑水肿，术后第72天脑水肿消退。组织学上，术后第16天出现亚急性细胞炎症反应，到第72天转变为慢性炎症反应。在BCNU负载聚合物的大脑半球接受放射治疗的组，仅检测到局限性的病理变化。在所有动物中，远离聚合物植入部位的大脑是正常的。在任何动物身上都没有看到神经或全身的有害影响。结论：聚酸酐聚合物PCPP：SA在灵长类动物脑内给药是安全的，同时放射治疗不会引起任何不良反应。这些实验结果对于理解PCPP：SA植入物在治疗脑部疾病中的临床效果很重要。
Sustained drug delivery by biodegradable polymer devices can increase the therapeutic efficacy of drugs by producing high local tissue concentrations over extended periods of time. lt has been shown previously that implantation of controlled-release polymers impregnated with the nitrosourea carmustine (BCNU) extended the period of survival in rats bearing the 9L glioma compared with similar rats treated with systemically administered BCNU. This study evaluated the effect on the monkey brain of interstitial delivery of BCNU by the biodegradable polyanhydride copolymer poly[bis(p-carboxyphenoxy)propane]anhydride (PCPP) and sebacic acid (SA) in a 20:80 formulation (PCPP:SA). The effect of combining interstitial BCNU with radiation therapy was also evaluated. Eighteen male cynomologus monkeys were randomly assigned to one of four groups: a control group; a group with implantation of empty polymer; a group with implantation of BCNU-loaded polymer; and a group with implantation of empty polymer in the right hemisphere and BCNU-loaded polymer in the left hemisphere, followed by irradiation. The effects were evaluated radiologically and histologically at specified times. A local reaction by the brain to the polymer was found, which was greater when the polymer contained BCNU. Local cerebral edema was observed radiographically on postoperative Day 14 and had resolved by Day 72. Histologically, a subacute cellular inflammatory response was seen on postoperative Day 16, which had changed to a chronic inflammatory response by Day 72. In the group with radiation therapy administered to the hemisphere bearing BCNU-loaded polymer, only localized pathological changes were detected. In all animals, brain distant from the polymer implantation site was normal. No neurological or general deleterious effects were seen in any of the animals. lt is concluded that the interstitial delivery of BCNU by the polyanhydride polymer PCPP:SA is safe in the primate brain and that concomitant radiation therapy did not lead to any adverse effects. These experimental findings are important to an understanding of the clinical effects of PCPP:SA implants in treating brain diseases.