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一种用于膀胱内化疗的基于水凝胶的表柔比星递送系统。

A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy.

作者信息

Liu Ching-Wen, Wu Yu-Tse, Lin Kai-Jen, Yu Tsan-Jung, Kuo Yu-Liang, Chang Li-Ching

机构信息

School of Pharmacy, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 807, Taiwan.

Department of Pathology, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, Taiwan.

出版信息

Molecules. 2016 Jun 1;21(6):712. doi: 10.3390/molecules21060712.

DOI:10.3390/molecules21060712
PMID:27258243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6274032/
Abstract

This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% ± 7.6% and 38.3% ± 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 ± 1.1 and 7.5 ± 0.3 μg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% ± 4.0% (EPI-AQ) and 34.1% ± 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer.

摘要

本研究旨在探讨载表柔比星明胶水凝胶（EPI-H）治疗浅表性尿路上皮癌的疗效。通过明胶与戊二醛的席夫碱交联制备水凝胶。EPI-H表现出高包封率（59.87%±0.51%）。与表柔比星水溶液（EPI-AQ）相比，EPI-H还增加了表柔比星在AY-27细胞中的蓄积；表柔比星阳性细胞计数分别为69.0%±7.6%和38.3%±5.8%。EPI-H对AY-27细胞的细胞毒性也比EPI-AQ更大；IC50值分别为13.1±1.1和7.5±0.3μg/mL。膀胱测压图显示，EPI-H降低了排尿峰值、阈值压力和排尿持续时间，并且比EPI-AQ更能增加膀胱顺应性。EPI-H增强了表柔比星在体内尿路上皮基底细胞中的渗透，而EPI-AQ仅作用于伞细胞。向F344大鼠荷瘤膀胱内灌注EPI-H可抑制肿瘤生长，诱导的半胱天冬酶-3表达水平高于EPI-AQ治疗；治疗的尿路上皮癌中半胱天冬酶-3阳性细胞数为13.9%±4.0%（EPI-AQ）和34.1%±1.0%（EPI-H）。EPI-H作为一种改进的方法，在膀胱癌膀胱内灌注治疗中给予表柔比星具有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/e82357cc67e9/molecules-21-00712-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/74977d3c72c0/molecules-21-00712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/e09521543473/molecules-21-00712-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/6049f66d985e/molecules-21-00712-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/f00b2c084e08/molecules-21-00712-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/c73c433dfd09/molecules-21-00712-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/17cf73bad5db/molecules-21-00712-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/e82357cc67e9/molecules-21-00712-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/74977d3c72c0/molecules-21-00712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/e09521543473/molecules-21-00712-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/6049f66d985e/molecules-21-00712-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/f00b2c084e08/molecules-21-00712-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/c73c433dfd09/molecules-21-00712-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/17cf73bad5db/molecules-21-00712-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ce/6274032/e82357cc67e9/molecules-21-00712-g007a.jpg

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