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不饱和游离脂肪酸乳剂经颈动脉输注可增强药物向大鼠脑内的递送。

Unsaturated free fatty acid emulsion infusion into carotid artery enhances drug delivery to the rat brain.

机构信息

Department of Radiology, College of Medicine, Pusan National University, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Busan, South Korea.

Institute for Research and Industry Cooperation, Pusan National University, Busan, South Korea.

出版信息

Brain Behav. 2023 Jun;13(6):e2994. doi: 10.1002/brb3.2994. Epub 2023 May 22.

DOI:10.1002/brb3.2994
PMID:37218399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10275518/
Abstract

AIMS

To determine whether the blood-brain barrier (BBB) opens to enhance drug delivery during the acute stage of unsaturated fat embolism.

METHODS

We infused oleic, linoleic, and linolenic acid emulsions through the right common carotid artery of rats, followed by trypan blue for gross and lanthanum for electron microscopic (EM) examination. Doxorubicin and temozolomide were also administered, and then the rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to semiquantitatively measure BBB opening. Desorption electrospray ionization-mass spectrometry (DESI-MS) imaging was used to evaluate drug delivery.

RESULTS

Trypan blue staining observed in each group 30 min after emulsion infusion increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic and linolenic acid groups showed weak staining over time. The hue and trypan blue analysis results were corroborative. EM showed tight junction opening, whereas DESI-MS imaging showed increased doxorubicin and temozolomide signal intensities in ipsilateral hemispheres of all three groups.

CONCLUSION

We demonstrated that oleic, linoleic, and linolenic acid emulsions opened the BBB, promoting drug delivery to the brain. Hue analysis and DESI-MS imaging are appropriate for analysis of doxorubicin and temozolomide concentrations in brain tissue.

摘要

目的

确定在不饱和脂肪栓塞的急性阶段，血脑屏障 (BBB) 是否开放以增强药物递送。

方法

我们通过大鼠右侧颈总动脉输注油酸、亚油酸和亚麻酸乳液，然后用台盼蓝进行大体检查，用镧进行电子显微镜 (EM) 检查。还给予多柔比星和顺铂，然后在 30 分钟、1 小时和 2 小时处死大鼠。用脱色电喷雾电离 - 质谱 (DESI-MS) 成像分析来半定量测量 BBB 开放程度。

结果

在乳液输注后 30 分钟，每个组中观察到的台盼蓝染色在 1 小时时增加，在 2 小时时减少。亚油酸和亚麻酸组的染色随时间减弱。色调和台盼蓝分析结果一致。EM 显示紧密连接打开，而 DESI-MS 成像显示三组的同侧半球中多柔比星和顺铂信号强度增加。

结论

我们证明了油酸、亚油酸和亚麻酸乳液打开了 BBB，促进了药物向大脑的递送。色调分析和 DESI-MS 成像适用于分析脑组织中多柔比星和顺铂的浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/3899a3a7d82c/BRB3-13-e2994-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/932d2a4e991f/BRB3-13-e2994-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/2560c311c281/BRB3-13-e2994-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/c24c0c78ac35/BRB3-13-e2994-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/42b8caebcdc3/BRB3-13-e2994-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/3899a3a7d82c/BRB3-13-e2994-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/932d2a4e991f/BRB3-13-e2994-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/2560c311c281/BRB3-13-e2994-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/c24c0c78ac35/BRB3-13-e2994-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/42b8caebcdc3/BRB3-13-e2994-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db5d/10275518/3899a3a7d82c/BRB3-13-e2994-g001.jpg

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本文引用的文献

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Doxorubicin concentration in brain remains high for one day after triolein emulsion infusion induced BBB opening.多柔比星在三油酸甘油酯乳剂诱导 BBB 开放后一天内仍在大脑中保持高浓度。
Int J Neurosci. 2020 Aug;130(8):770-776. doi: 10.1080/00207454.2019.1705809. Epub 2019 Dec 23.
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