Contribution of both olfactory and systemic pathways for brain targeting of nimodipine-loaded lipo-pluronics micelles: in vitro characterization and in vivo biodistribution study after intranasal and intravenous delivery.
Contribution of both olfactory and systemic pathways for brain targeting of nimodipine-loaded lipo-pluronics micelles: in vitro characterization and in vivo biodistribution study after intranasal and intravenous delivery.
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DOI：
10.1080/10717544.2016.1236848
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发表时间：
2016-11
期刊：
影响因子：
6
通讯作者：
Basalious EB
中科院分区：
文献类型：
--
作者：
Rashed HM;Shamma RN;Basalious EB
尼莫地平（NM）是FDA批准的唯一治疗蛛网膜下腔出血引起的血管痉挛的药物。NM由于其低水溶性和广泛的首过代谢而具有差的口服生物利用度（5-13%）。本研究的目的是开发放射性标记的NM负载的LPM，并测试其延长其循环时间，降低其给药频率并最终将其靶向脑组织的能力。用连二亚硫酸钠直接标记法，用99 mTc标记NM。研究了影响放射性标记产率的不同反应条件。在静脉内和鼻内给药后，将最佳NM负载的LPM制剂在血液、心脏和脑组织中的体内药代动力学行为与NM溶液进行比较。结果表明，与99 mTc-NM溶液给药相比，99 mTc-NM负载LPM给药后小鼠心脏中的放射性百分比（%ID/g）降低，这非常有利于最小化心血管副作用。结果还表明，与静脉注射99 mTc-NM溶液相比，静脉注射99 mTc-NM负载的LPM后血液和脑中的%ID/g在所有采样间隔均较高。这对于神经血管疾病的治疗将是非常有益的。鼻内给药后NM的脑靶向效率为1872.82%。载NM的LPM的药物溶解度的显著增加、增强的药物吸收和长循环时间可能有希望改善NM的鼻内和肠胃外递送。
Nimodipine (NM) is the only FDA-approved drug for treating subarachnoid hemorrhage induced vasospasm. NM has poor oral bioavailability (5–13%) due to its low aqueous solubility, and extensive first pass metabolism. The objective of this study is to develop radiolabeled NM-loaded LPM and to test its ability prolong its circulation time, reduce its frequency of administration and eventually target it to the brain tissue. NM was radiolabeled with 99mTc by direct labeling method using sodium dithionite. Different reaction conditions that affect the radiolabeling yield were studied. The in vivo pharmacokinetic behavior of the optimum NM-loaded LPM formulation in blood, heart, and brain tissue was compared with NM solution, after intravenous and intranasal administration. Results show that the radioactivity percentage (%ID/g) in the heart of mice following administration of 99mTc-NM loaded LPM were lower compared with that following administration of 99mTc-NM solution, which is greatly beneficial to minimize the cardiovascular side effects. Results also show that the %ID/g in the blood, and brain following intravenous administration of 99mTc-NM-loaded LPM were higher at all sampling intervals compared with that following intravenous administration of 99mTc-NM solution. This would be greatly beneficial for the treatment of neurovascular diseases. The drug-targeting efficiency of NM to the brain after intranasal administration was calculated to be 1872.82%. The significant increase in drug solubility, enhanced drug absorption and the long circulation time of the NM-loaded LPM could be promising to improve nasal and parenteral delivery of NM.
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影响因子：
6
作者：
Abd-Elal, Radwa M. A.;Shamma, Rehab N.;Bendas, Ehab R.
通讯作者：
Bendas, Ehab R.
影响因子：
5.8
作者：
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通讯作者：
Shamma, Rehab N.
DOI：
10.1007/s10967-012-2168-1
发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
1.8
作者：
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通讯作者：
Goracinova, Katerina