Sawyer Andrew J, Piepmeier Joseph M, Saltzman W Mark
Department of Biomedical Engineering, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Yale J Biol Med. 2006 Dec;79(3-4):141-52.
Despite advances in diagnostic imaging and drug discovery, primary malignant brain tumors remain fatal. Median survival for patients with the most severe forms is rarely past eight months. The severity of the disease and the lack of substantial improvement in patient survival demand that new approaches be explored in drug delivery to brain tumors. Recently, local delivery of chemotherapy to brain tumors has provided a way to circumvent the blood-brain barrier, allowing delivery of chemotherapy drugs directly to malignant cells in the brain. Two methods of local delivery have been developed: polymeric-controlled release and convection-enhanced delivery. Controlled release utilizes degradable or non-degradable polymers as carriers of chemotherapy; polymer implants or microparticles are implanted locally to introduce a sustained source of drug for periods of days or months. Convection-enhanced delivery employs the bulk flow of drugs dissolved in fluid, which is introduced intracranially using a catheter and pump. The convective fluid flow is capable of delivering drugs great distances within the brain, potentially treating invasive cells at a distance from the catheter infusion site. These two new delivery strategies are capable of delivering both standard chemotherapeutic drugs and new methods of anti-cancer therapy. Taken individually, or used in tandem, they represent a potential revolution in brain cancer treatment.
尽管在诊断成像和药物研发方面取得了进展,但原发性恶性脑肿瘤仍然是致命的。最严重形式的患者的中位生存期很少超过八个月。该疾病的严重性以及患者生存率缺乏实质性改善,要求在脑肿瘤药物递送方面探索新方法。最近,向脑肿瘤局部递送化疗药物提供了一种绕过血脑屏障的方法,使得化疗药物能够直接递送至脑内的恶性细胞。已经开发出两种局部递送方法:聚合物控释和对流增强递送。控释利用可降解或不可降解的聚合物作为化疗药物的载体;聚合物植入物或微粒被局部植入以引入持续数天或数月的药物来源。对流增强递送利用溶解在流体中的药物的大量流动,使用导管和泵将其颅内注入。对流流体流动能够在脑内远距离递送药物,有可能治疗距导管输注部位有一定距离的侵袭性细胞。这两种新的递送策略能够递送标准化疗药物和新的抗癌治疗方法。单独使用或联合使用,它们代表了脑癌治疗的一场潜在革命。