Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue.
Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue.
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DOI：
10.1007/s11060-014-1421-6
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发表时间：
2014-05
影响因子：
3.9
通讯作者：
Straubinger, Robert M.
中科院分区：
文献类型：
--
作者：
Joshi, Shailendra;Singh-Moon, Rajinder P.;Wang, Mei;Chaudhuri, Durba B.;Holcomb, Mark;Straubinger, Ninfa L.;Bruce, Jeffrey N.;Bigio, Irving J.;Straubinger, Robert M.
关键词：
根据经验，暂时性脑灌注不足（TCH）已被用于辅助动脉内（IA）药物递送至脑肿瘤。许多神经和心血管干预期间都会发生脑血流量 (CBF) 的短暂（< 3 分钟）减少，并且最近已用于更好地将 IA 药物靶向脑肿瘤。在本实验中，我们评估了 TCH 是否可以提高阳离子脂质体 IA 递送的有效性。将由 1:1 DOTAP:PC（二油酰基三甲基铵丙烷：磷脂酰胆碱）组成的阳离子脂质体给予三组 Sprague Dawley 大鼠。在第一组中，我们测试了血流量减少对阳离子脂质体 IA 递送的影响。在第二组中，我们比较了相同剂量的 TCH 辅助 IA 脂质体递送与静脉内 (IV) 给药。在第三组中，我们评估了TCH辅助分娩后四小时大脑中阳离子脂质体的保留情况。脂质体含有近红外染料DilC18(7)，其浓度可以通过漫反射光谱在体内测量。与正常血流期间注射相比，TCH 期间 IA 注射阳离子脂质体可将其递送量增加约四倍。光学药代动力学测量表明，相对于静脉注射，TCH 期间 IA 注射阳离子脂质体产生的组织浓度高出 100 倍。单次 IA 注射后四小时，阳离子脂质体保留在脑组织中。幸存动物的神经功能没有明显受损。 CBF 的瞬时减少显着增加了大脑中阳离子脂质体的 IA 递送。 IA注射和TCH同时注射后，高浓度的脂质体可以被递送至脑组织，而IV注射后则检测不到任何脂质体。 IA-TCH 注射耐受性良好，并且在 IA 给药后，阳离子脂质体保留至少 4 小时。这些结果应该鼓励化疗药物的阳离子脂质体制剂的开发及其在 TCH 期间的 IA 递送。
Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (< 3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery vs. intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain four hours after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. IA injections of cationic liposomes during TCH increased their delivery approximately four-fold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue four hours after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 hours after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH.
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DOI：
10.1097/01.wcb.0000107731.66603.18
发表时间：
2004-03-01
影响因子：
6.3
作者：
Joshi, S;Wang, M;Hartl, T
通讯作者：
Hartl, T
影响因子：
1.9
作者：
Mourant, JR;Bigio, IJ;Miller, HD
通讯作者：
Miller, HD
影响因子：
8.8
作者：
Joshi, S;Wang, M;Pile-Spellman, J
通讯作者：
Pile-Spellman, J
影响因子：
3.3
作者：
Yamane, Takashi;Kaneko, Akihiro;Mohri, Makoto
通讯作者：
Mohri, Makoto
影响因子：
2.9
作者：
WALLACE, S;CARRASCO, CH;GIANTURCO, C
通讯作者：
GIANTURCO, C