Tamargo R J, Myseros J S, Epstein J I, Yang M B, Chasin M, Brem H
Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Cancer Res. 1993 Jan 15;53(2):329-33.
The administration of drugs directly into the central nervous system using polymers as drug carriers may improve the treatment of malignant brain tumors. In this study, the effect of the interstitial, localized delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) incorporated into controlled release polymers implanted adjacent to the 9L gliosarcoma was assessed in s.c. and intracranial (i.c.) models. In the s.c. experiment, the 9L gliosarcoma was implanted in the flank of rats and subsequently treated with BCNU either (a) delivered in controlled release polymers inserted adjacent to the tumor or (b) administered systemically by i.p. injections or by controlled release polymers inserted at a site distant from the tumor. The interstitial release of BCNU adjacent to the tumor in the flank resulted in a significant tumor growth delay of 16.3 days, as compared to a growth delay of 9.3 and 11.2 days obtained with the systemic administration of BCNU. In the i.c. experiment, the 9L gliosarcoma was implanted in the brain of Fischer 344 rats and treated either (a) with controlled release polymers containing BCNU inserted into the brain or (b) with the systemic i.p. administration of BCNU. The interstitial release of BCNU in the brain resulted in a significant 5.4- to 7.3-fold increased survival, compared with a 2.4-fold increased survival after the systemic administration of the same dose of BCNU. The two groups with i.c. tumors treated interstitially had 17 and 42% cures, but no long-term cures were obtained in the group treated with systemic therapy. The localized, controlled delivery of chemotherapeutic agents in the s.c. tissues and in the brain via polymeric carriers may be more effective than standard systemic chemotherapy. This approach could be used to deliver a wide variety of agents into the central nervous system to treat diverse neuropathological conditions which remain refractory to systemic therapy.
使用聚合物作为药物载体将药物直接注入中枢神经系统可能会改善恶性脑肿瘤的治疗效果。在本研究中，评估了将1,3-双(2-氯乙基)-1-亚硝基脲(BCNU)掺入植入9L胶质肉瘤附近的控释聚合物中进行间质局部给药在皮下和颅内(i.c.)模型中的效果。在皮下实验中，将9L胶质肉瘤植入大鼠侧腹，随后用BCNU进行治疗，治疗方式包括：(a) 通过插入肿瘤附近的控释聚合物给药；(b) 通过腹腔注射进行全身给药，或通过插入远离肿瘤部位的控释聚合物给药。与通过BCNU全身给药获得的9.3天和11.2天的生长延迟相比，侧腹肿瘤附近BCNU的间质释放导致肿瘤生长显著延迟16.3天。在颅内实验中，将9L胶质肉瘤植入Fischer 344大鼠脑中，并进行如下治疗：(a) 插入含BCNU的控释聚合物到脑中；(b) 腹腔注射BCNU进行全身给药。与相同剂量BCNU全身给药后生存率提高2.4倍相比，脑中BCNU的间质释放导致生存率显著提高5.4至7.3倍。两组颅内肿瘤间质治疗组的治愈率分别为17%和42%，但全身治疗组未获得长期治愈。通过聚合物载体在皮下组织和脑中进行化疗药物的局部控释可能比标准全身化疗更有效。这种方法可用于将多种药物输送到中枢神经系统，以治疗对全身治疗仍有抗性的各种神经病理状况。
