Development of microspheres for neurological disorders: From basics to clinical applications
Development of microspheres for neurological disorders: From basics to clinical applications
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DOI：
10.1016/s0168-3659(99)00250-3
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发表时间：
2000-03-01
影响因子：
10.8
通讯作者：
Menei, P
中科院分区：
文献类型：
--
作者：
Benoit, JP;Faisant, N;Menei, P
药物输送到中枢神经系统仍然是一个具有挑战性的研究领域的基础和临床神经科学家。由于脑毛细血管内皮壁的可忽略的渗透性，许多药物通常被排除在血液到布兰的转移之外，脑毛细血管内皮壁构成了体内的血脑屏障。几年来，我们已经探索了治疗剂的微胶囊化的潜在应用，以提供中枢神经系统中的局部控制药物释放。由于它们的尺寸，这些微粒可以通过立体定向容易地植入大脑的离散，精确和功能区域，而不会损伤周围组织。这种类型的植入避免了通过开放手术插入大植入物的不便，并且如果需要可以重复。我们已经建立了聚（丙交酯-共-乙交酯）微球与脑组织的相容性。目前，最发达的应用涉及神经病学和神经肿瘤学，分别将神经营养因子和抗有丝分裂药物局部递送到神经退行性病变和脑肿瘤中。本课题组已包封的药物包括神经生长因子（NGF）、5-氟尿嘧啶（5-FU）、碘尿苷和卡氮芥（BCNU）。已对每种药物进行了临床前研究。以神经生长因子的研究为例。在新诊断的胶质母细胞瘤患者中进行了I/II期临床试验，以评估颅内植入5-FU载药微球的潜力。(C)2000 Elsevier Science B. V.保留所有权利。
Drug delivery to the central nervous system remains a challenging area of investigation for both basic and clinical neuroscientists. Numerous drugs are generally excluded from blood to blain transfer due to the negligible permeability of the brain capillary endothelial wall, which makes up the blood brain barrier in vivo. For several years, we have explored the potential applications of the microencapsulation of therapeutic agents to provide local controlled drug release in the central nervous system. Due to their size, these microparticles can be easily implanted by stereotaxy in discreet, precise and functional areas of the brain without damaging the surrounding tissue. This type of implantation avoids the inconvenient insertion of large implants by open surgery and can be repeated if necessary. We have established the compatibility of poly(lactide-co-glycolide) microspheres with brain tissues. Presently, the most developed applications concern Neurology and Neuro-oncology, with local delivery of neurotrophic factors and antimitotic drugs into neurodegenerative lesions and brain tumours, respectively. The drugs that had been encapsulated by our group included nerve growth factor (NGF), 5-fluorouracil (5-FU), idoxuridine and BCNU. Preclinical studies have been performed with each drug. Studies with NGF are reported as an example. A phase I/II clinical trial has been carried out in patients with newly diagnosed glioblastomas to assess the potentialities of 5-FU-loaded microspheres when intracranially implanted. (C) 2000 Elsevier Science B.V. All rights reserved.