1.Lexiscan can open the blood-brain barrier temporarily and reversibly
Cancan CHANG ; Yang DUAN ; Benqiang YANG ; Jun ZHOU ; Hongyi LI ; Zhihua XU ; Sen LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(11):741-744
Objective To evaluate the opening level and optimal time window of the blood-brain barrier induced by adenosine A2 receptor agonist ( Lexiscan) via dynamic enhanced MRI. Methods Twen-ty New Zealand white rabbits were divided into experiment group ( group A, n=10) and control group ( group B, n=10) . Rabbits in group A were injected with Lexiscan and rabbits in group B were injected with physiological salt via ear vein, then the coronary scanning was performed. Contrast enhanced MRI was performed at different time points ( 5, 10, 15, 20 min, and then every 10 min, until 2 h) following the in-fusion of Gd-diethylene triamine pentaacetic acid (DTPA). The signal intensity (SI) of region of interest ( ROI) was measured and the percent enhancement of SI was calculated. Evens blue staining results in brain tissues were observed. Pair t test was used to analyze the data. Results The percent enhancement of SI in group A significantly increased to (40. 93±3.70)% at 5 min, reached the maximum of (43.03±3.62)% at 30 min, slowly decreased until 50 min, and got to a stable level at almost 80 min. At each time point, the per-cent enhancement of SI in group A was significantly higher than that in group B ( t values:6.88-20.28, all P<0. 05) . The staining was evident in group A. Conclusions Lexiscan can open blood-brain barrier tem-porarily and reversibly, and the optimal opening time window is 10-50 min post-injection.
2.Study on the intestinal absorption characteristics of saikosaponins
Yazhi WANG ; Qiyi WANG ; Wenzhong FENG ; Shuangshuang CHEN ; Xinguang SUN ; Lijuan ZHOU ; Yan ZHANG ; Jianyong ZHANG ; Cancan DUAN
China Pharmacy 2023;34(14):1681-1685
OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model, using accumulative absorption amount (Q) and absorption rate constant (Ka) as indexes, UHPLC-MS/MS technique as a method, the absorption of saikosaponin A, B2, C, D and F from total saponins of Bupleurum chinense (8 g/mL, by crude drug) in the duodenum, jejunum and ileum was detected. RESULTS The correlation coefficients (r) of the regression equations for the absorption of saikosaponins A, B2, C and F in the duodenum, jejunum and ileum were all higher than 0.95, while the r of saikosaponin D in the above intestinal segments was lower than 0.95; compared with the absorption of the same composition in the duodenum, the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min, as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased (P<0.05). CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum, jejunum and ileum; among them, saikosaponin A, B2, C and F are linearly absorbed, which conforms to the zero-order absorption characteristics, but saikosaponin D shows non- linear absorption.
3.Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles.
Yan YAN ; Cancan DU ; Xixi DUAN ; Xiaohan YAO ; Jiajia WAN ; Ziming JIANG ; Zhongyu QIN ; Wenqing LI ; Longze PAN ; Zhuoyu GU ; Fazhan WANG ; Ming WANG ; Zhihai QIN
Acta Pharmaceutica Sinica B 2022;12(2):939-951
The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.