Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection.
Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection.
复制标题
DOI：
10.1007/s11060-014-1584-1
复制
发表时间：
2014-12
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;Wang, Mei;Chaudhuri, Durba B.;Ellis, Jason A.;Bruce, Jeffrey N.;Bigio, Irving J.;Straubinger, Robert M.
关键词：
快速的首过吸收药物对于增加动脉内注射（IA）后的组织沉积是必要的。在这里，我们测试了纳米粒脂质体载体的脑组织沉积是否可以通过协调操纵脂质体表面电荷和生理参数来增强，例如在短暂性脑灌注不足（TCH）期间注射IA。聚焦超声对三组大鼠血脑屏障（BBB）造成不同程度的破坏。然后比较注射IA联合TCH后阴离子、阳离子和电荷中性脂质体的脑组织保留情况。脂质体含有不可交换的碳氰膜光学标记，可以用漫反射光谱（DRS）定量或通过多光谱成像可视化。每次注射脂质体后，实时获得脑内浓度-时间曲线。在观察到阳离子脂质体比其他脂质体在所有三组中更大的组织滞留后，我们测试了C6荷瘤大鼠对阳离子脂质体的摄取。死后切片的DRS和多光谱成像显示，与非肿瘤的对侧半球相比，C6脑肿瘤的脂质体摄取增加。我们得出的结论是，在健康和C6荷瘤大鼠中，使用IA注射阳离子脂质体制剂可以增强脂质体的区域沉积，而不会破坏血脑屏障。
Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injection during transient cerebral hypoperfusion (TCH). Different degrees of blood-brain barrier (BBB) disruption were induced by focused ultrasound in three sets of Sprague Dawley rats. Brain tissue retention was then compared for anionic, cationic, and charge-neutral liposomes after IA injection combined with TCH. The liposomes contained a non-exchangeable carbocyanine membrane optical label that could be quantified using diffuse reflectance spectroscopy (DRS) or visualized by multispectral imaging. Real-time concentration-time curves in brain were obtained after each liposomal injection. Having observed greater tissue retention of cationic liposomes compared to other liposomes in all three groups, we tested uptake of cationic liposomes in C6 tumor bearing rats. DRS and multispectral imaging of postmortem sections revealed increased liposomal uptake by the C6 brain tumor as compared to non-tumor contralateral hemisphere. We conclude that regional deposition of liposomes can be enhanced without BBB disruption using IA injection of cationic liposomal formulations in healthy and C6 tumor bearing rats.
登录
查看更多内容
影响因子：
1.9
作者：
Mourant, JR;Bigio, IJ;Miller, HD
通讯作者：
Miller, HD
影响因子：
3.5
作者：
Hossain, Shaolie S.;Hughes, Thomas J. R.;Decuzzi, Paolo
通讯作者：
Decuzzi, Paolo
影响因子：
8.8
作者：
Joshi, S;Wang, M;Pile-Spellman, J
通讯作者：
Pile-Spellman, J
用于脑药物输送的渗透素功能化 PEG-PLA 纳米颗粒
影响因子：
5.8
作者：
Xia, Huimin;Gao, Xiaoling;Chen, Hongzhuan
通讯作者：
Chen, Hongzhuan
影响因子：
4.5
作者：
Zhao, Ming;Chang, Jin;Li, Anmin
通讯作者：
Li, Anmin