Enhanced Doxorubicin Delivery to the Brain Administered Through Glutathione PEGylated Liposomal Doxorubicin (2B3-101) as Compared with Generic Caelyx,®/Doxil®A Cerebral Open Flow Microperfusion Pilot Study
Enhanced Doxorubicin Delivery to the Brain Administered Through Glutathione PEGylated Liposomal Doxorubicin (2B3-101) as Compared with Generic Caelyx,®/Doxil®A Cerebral Open Flow Microperfusion Pilot Study
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DOI：
10.1002/jps.23994
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发表时间：
2014-07-01
影响因子：
3.8
通讯作者：
Sinner, Frank
中科院分区：
文献类型：
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作者：
Birngruber, Thomas;Raml, Reingard;Sinner, Frank
神经保护血脑屏障（BBB）使许多候选药物在中枢神经系统中低于治疗水平。谷胱甘肽聚乙二醇脂质体阿霉素（2B3-101）已被开发用于安全增强阿霉素对脑肿瘤的递送。然而，使用常规技术尚不能可靠地测量细胞外脑液中的阿霉素浓度。脑开放血流微灌注（cOFM）是最近发展起来的一种采样技术，可以监测大脑中独立于分子量和亲脂性的药物浓度。结合cOFM采样，荧光素钠（NaF）被用作血脑屏障完整性的标记物。大鼠静脉注射7mg /kg 2B3-101或聚乙二醇化脂质体阿霉素（通用Caelyx (R)）。给药后5 h进行血液和cOFM采样。监测脑内NaF浓度，并保持低浓度，表明血脑屏障完好。给予2B3-101后，阿霉素脑血比比比通用药Caelyx高4.8倍（p = 0.0016）。总之，通过使用cOFM可以证明2B3-101导致脑内阿霉素浓度升高而不影响血脑屏障的完整性。(3)中国医药科学，2014,(3):1 - 4
The neuroprotective blood-brain barrier (BBB) keeps many drug candidates below therapeutic levels in the central nervous system. Glutathione PEGylated liposomal doxorubicin (2B3-101) has been developed to safely enhance the delivery of doxorubicin to brain tumors. However, doxorubicin concentration in extracellular brain fluid cannot yet be reliably measured using conventional techniques. Cerebral open flow microperfusion (cOFM), a recently developed sampling technique, allows monitoring of drug concentrations in the brain independent of molecular weight and lipophilicity. In combination with cOFM sampling, sodium fluorescein (NaF) is used as a marker for BBB integrity. Rats received one intravenous dose of 7 mg/kg of either 2B3-101 or PEGylated liposomal doxorubicin (generic Caelyx (R)). Blood and cOFM sampling was performed for 5 h after dose injection. NaF concentration in the brain was monitored and remained low indicating an intact BBB. The brain-to-blood ratio of doxorubicin was 4.8-fold higher after administration of 2B3-101 as compared with generic Caelyx (R) (p = 0.0016). In conclusion, by using cOFM it was possible to show that 2B3-101 leads to enhanced doxorubicin concentration in the brain without affecting the BBB integrity. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1945-1948, 2014