Retro-convection enhanced delivery to increase blood to brain transfer of macromolecules.
Retro-convection enhanced delivery to increase blood to brain transfer of macromolecules.
复制标题
逆向对流增强输送，以增加大分子从血液到大脑的转移。
DOI：
10.1016/j.brainres.2006.10.041
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
SzokaJr,FrancisC
中科院分区：
文献类型：
--
作者：
Huynh,GraceH;Ozawa,Tomoko;Deen,DennisF;Tihan,Tarik;SzokaJr,FrancisC
已经开发了逆向对流增强递送（R-CED）方法以改善静脉内施用的治疗剂进入实体脑肿瘤内。R-CED使用渗透梯度通过植入的微透析导管以受控方式抽取脑间质液（ISF）。撤回ISF增加了正常脑中的局部组织比重，并增加了正常脑和原位9 L肿瘤中静脉内伊文思蓝（EB）白蛋白外渗的两倍。R-CED还使9 L肿瘤中70 nm荧光脂质体的外渗增加五倍。因此，跨膜渗透梯度诱导血液中的物质移动到组织实质中。去除探针后，正常脑中R-CED对EB-白蛋白外渗的影响程度在1.5小时内降低至对照值;然而，该影响在肿瘤中持续超过6小时。在R-CED后6小时或2周，没有证据表明神经元的组织学损伤。这些研究确立了应用R-CED增加全身给药药物在正常组织-肿瘤边缘以及中央肿瘤核心中的分布的可行性，提出了改善抗肿瘤药物疗效的可能性。
A retro-convection enhanced delivery (R-CED) method has been developed to improve the entry of intravenously administered therapeutics within solid brain tumors. R-CED uses an osmotic gradient to withdraw brain interstitial fluid (ISF) in a controlled manner via an implanted microdialysis catheter. Withdrawal of ISF increases the local tissue specific gravity in normal brain and increases twofold the extravasation of intravenous Evans blue (EB) albumin in normal brain and in an orthotopic 9L tumor. R-CED also increases the extravasation of 70 nm fluorescent liposomes fivefold in the 9L tumor. Thus the transmembrane osmotic gradient induces movement of substances in the blood into the tissue parenchyma. Following probe removal, the magnitude of the R-CED effect on EB-albumin extravasation decreases to control values within 1.5 h in normal brain; however, the effect persists beyond 6 h in the tumor. There was no evidence of histologic damage to the neurons at either 6 h or 2 weeks after R-CED. These studies establish the feasibility of applying R-CED to increase the distribution of systemically administered drugs in both the normal tissue–tumor margin as well as in the central tumor core, holding forth the possibility of improved antitumor drug efficacy.