In vivo release from a drug delivery MEMS device
In vivo release from a drug delivery MEMS device
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DOI：
10.1016/j.jconrel.2004.08.018
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发表时间：
2004-11-24
影响因子：
10.8
通讯作者：
Cima, MJ
中科院分区：
文献类型：
--
作者：
Li, YW;Shawgo, RS;Cima, MJ
为了最大限度地发挥药物治疗的效果，设计了一种药物输送微电子机械系统(MEMS)装置，用于释放多种物质的复杂轮廓。该装置的基础是蚀刻在硅衬底上的微型储液器，其中含有个别剂量的药物。每一剂量都是通过覆盖储集层的金膜的电化学溶解来释放的。这项研究首次报道了该装置的活体操作。两种示踪分子荧光素染料和放射性标记甘露醇和一种放射性标记化疗药物卡莫司汀(BCNU)在大鼠皮下释放。选择BCNU是因为需要改善化疗对恶性肿瘤的直接输送。用荧光法测定给药装置释放荧光素染料的空间分布，用液体闪烁计数法评价C-14标记甘露醇释放的时间分布，用加速器质谱仪(AMS)评价C-14标记BCNU释放的时间分布。比较注射对照和激活装置的释药曲线。体内染料释放结果显示，激活1h后，装置周围的侧翼组织中有高浓度的荧光素。从给药装置中释放的C-14标记甘露醇可迅速从大鼠尿液中清除(1天)。C-14标记的BCNU从活化装置中的体内释放速度比注射和体外对照略慢，达到稳态血浆C-14浓度的时间约为1h，这些结果表明该给药装置能够实现各种具有明确时间分布的化合物的局部释放。(C)2004爱思唯尔B.V.保留所有权利。
A drug delivery microelectromechanical systems (MEMS) device was designed to release complex profiles of multiple substances in order to maximize the effectiveness of drug therapies. The device is based on micro-reservoirs etched into a silicon substrate that contain individual doses of drug. Each dose is released by the electrochemical dissolution of the gold membrane that covers the reservoir. The first in vivo operation of this device was reported in this study. Subcutaneous release was demonstrated in rats using two tracer molecules, fluorescein dye and radiolabeled mannitol, and one radiolabeled chemotherapeutic agent, carmustine (BCNU). BCNU was chosen because of the need to improve the direct delivery of chemotherapy to malignant tumors. The spatial profile of fluorescein dye release from the drug delivery device was evaluated by fluorimetry, the temporal profile of C-14 labeled mannitol release was evaluated by liquid scintillation counting, and the temporal profile of C-14 labeled BCNU release was evaluated by accelerator mass spectrometry (AMS). Release profiles obtained from injected controls were compared with those from activated devices. The in vivo dye release results showed high concentration of fluorescein in the flank tissue surrounding the devices 1 h after activation. The C-14 labeled mannitol released from the drug delivery devices was rapidly cleared (1 day) from the rat urine. in vivo release of C-14 labeled BCNU from activated devices showed slightly slower kinetics than the injected and in vitro controls, and the time to reach the steady-state plasma C-14 concentration was on the order of 1 h. All these results demonstrated the capability of this drug delivery device to achieve localized delivery of various compounds with well-defined temporal profiles. (C) 2004 Elsevier B.V. All rights reserved.