Injectable chemotherapeutic microspheres and glioma I: Enhanced survival following implantation into the cavity wall of debulked tumors
Injectable chemotherapeutic microspheres and glioma I: Enhanced survival following implantation into the cavity wall of debulked tumors
复制标题
DOI：
10.1023/a:1007576405039
复制
发表时间：
2000-07-01
影响因子：
3.7
通讯作者：
Bartus, RT
中科院分区：
文献类型：
--
作者：
Emerich, DF;Winn, SR;Bartus, RT
目的.植入生物可降解聚合物提供了一种强有力的方法，提供高，持续浓度的化疗药物的脑肿瘤。本研究检查了可注射聚合物微球的能力，其被配制成释放卡铂或BCNU 2-3周，以提高切除的神经胶质瘤的啮齿动物模型的存活率。将大鼠神经胶质瘤（RG 2）细胞植入大鼠的皮质中，并在手术切除之前使其生长10天。大鼠被给予仅手术切除、团注（100 μ g）或含有10、50或100 μ g卡铂或BCNU的微球。将微球通过皮下注射直接植入手术腔或沿手术腔周围沿着组织中。各治疗组生存率顺序为：不切除<单纯切除<单次化疗<缓释化疗。卡铂和BCNU在这方面没有差异，在每种情况下，持续释放实现的生存率提高与剂量相关。然而，当微球植入切除腔的周边壁中时，与植入腔本身中相比，卡铂实现的增强的存活率显著更高。卡铂植入物沿着切除周边产生的生存率提高与肿瘤再生长的显著衰减相关。最后，在一项单独的研究中，在非肿瘤脑，原子吸收分光光度法显示，虽然微球产生显着延长组织水平的卡铂相对于推注，卡铂扩散仅限于脑组织延伸主要从注射部位0.5毫米。这些数据表明：（1）化疗的持续递送上级肿瘤切除后的等效推注剂量，和（2）将持续释放微球直接注射到生长的肿瘤块周围的组织中可以提供优于注射到手术腔中的效果。他们还表明，这种方法在人体中的成功实施可能需要改善植入部位的有限空间药物扩散的措施或环境。
Purpose. Implantation of biodegradable polymers provides a powerful method to deliver high, sustained concentrations of chemotherapeutics to brain tumors. The present studies examined the ability of injectable polymeric microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rodent model of surgically-resected glioma.Methods. Rat glioma (RG2) cells were implanted into the cortex of rats and allowed to grow for 10 days prior to surgical resection. Rats were given either surgical resection only, bolus injection (100 mu g) or microspheres containing 10, 50, or 100 mu g of carboplatin or BCNU. The microspheres were implanted, via hypodermic injection, either directly into the surgical cavity or into the tissue along the perimeter of the cavity.Results. The order of survival among treatment groups was: no resection < resection only < bolus chemotherapy < sustained release chemotherapy. Carboplatin and BCNU did not differ in this respect and in each case, the enhanced survival achieved with sustained release was dose-related. However, the enhanced survival achieved with carboplatin was substantially greater when the microspheres were implanted into the perimeter wall of the resection cavity, compared to implantation into the cavity itself. The enhanced survival produced by carboplatin implants along the resection perimeter was associated with a significant attenuation of regrowth of the tumor. Finally, in a separate study in non-tumor brain, atomic absorption spectrophotometry revealed that while the microspheres produced significantly prolonged tissue levels of carboplatin relative to a bolus injection, carboplatin diffusion was limited to brain tissue extending primarily 0.5 mm from the injection site.Conclusions. These data demonstrate: (1) that sustained delivery of chemotherapy is superior to equipotent bolus doses following tumor resection, and (2) that direct injection of sustained release microspheres into the tissue surrounding a growing tumor mass may provide superior effects over injections into the surgical cavity. They also suggest that successful implementation of this approach in humans may require measures or circumstances that improve upon the limited spatial drug diffusion from the implantation site.