Docosahexaenoic acid-mediated, targeted and sustained brain delivery of curcumin microemulsion.
Docosahexaenoic acid-mediated, targeted and sustained brain delivery of curcumin microemulsion.
复制标题
DOI：
10.1080/10717544.2016.1233593
复制
发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Devarajan PV
中科院分区：
文献类型：
--
作者：
Shinde RL;Devarajan PV
我们公开了姜黄素(Cur)与富含二十二碳六烯酸(DHA)油(Cur DHA ME)的微乳(ME)，用于定向给药到大脑。适合静脉和鼻腔给药的Cur(5 mg/mLCur Capmul ME)分别加入和不加入富含DHA的油(Cur Capmul ME)，MES显示负Zeta电位，颗粒大小 <；20 nm，稳定性好。在静脉注射后，MES显示出较高的脑浓度，Cur DHA ME显示出比Cur溶液高2.8倍的Cmax。此外，即使在24 h也表现出较高的持续浓度，分别是Cur溶液和Cur Capmul ME的8倍和2倍。然而，与相应的静脉给药相比，鼻腔给药后的脑浓度明显更高，从更高的Cmax和AUC可以明显看出这一点，这意味着鼻对脑靶向。Cur DHA ME的高脑浓度归因于DHA介导的跨血脑屏障(BBB)转运的靶向效率。组织病理学和鼻部毒性证实MES是安全的。用Cur DHA MES和空白DHA ME观察了DHA对人胶质母细胞瘤U-87 mg细胞株的体外浓度依赖性细胞毒作用，提示DHA具有抗癌作用。因此，Cur DHA ME的IC50值极低(3.755 ± 0.24 ng/mL)归因于Cur和DHA在ME中的协同作用。Cur DHA ME在24 h达到的Cur浓度，在U-87 mg细胞系中转化为 >；66倍(鼻内)和 >；21倍(静脉)的IC50值，表明Cur DHA ME在两种途径治疗脑癌方面都有很大的前景。
We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHA-rich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size <20 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher Cmax than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8- and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher Cmax and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood–brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentration-dependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to >66-fold(intranasal) and >21–fold (intravenous) the IC50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.
登录
查看更多内容
影响因子：
10.8
作者：
Dobrovoiskaia, Marina A.;Clogston, Jeffrey D.;Neun, Barry W.;Hall, Jennifer B.;Patri, Anil K.;McNeil, Scott E.
通讯作者：
McNeil, Scott E.
DOI：
10.3945/jn.108.096016
发表时间：
2008-12
期刊：
The Journal of nutrition
影响因子：
--
作者：
Lukiw WJ;Bazan NG
通讯作者：
Bazan NG
影响因子：
4.9
作者：
Ganta, Srinivas;Amiji, Mansoor
通讯作者：
Amiji, Mansoor
影响因子：
2.1
作者：
Jogani, Viral V.;Shah, Pranav J.;Misra, Ambikanandan R.
通讯作者：
Misra, Ambikanandan R.
影响因子：
4.1
作者：
Harvey, Kevin A.;Xu, Zhidong;Siddiqui, Rafat A.
通讯作者：
Siddiqui, Rafat A.