A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy

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 incre...

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Main Authors: Ching-Wen Liu, Yu-Tse Wu, Kai-Jen Lin, Tsan-Jung Yu, Yu-Liang Kuo, Li-Ching Chang
Format: Article
Language:English
Published: MDPI AG 2016-06-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/21/6/712
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author Ching-Wen Liu
Yu-Tse Wu
Kai-Jen Lin
Tsan-Jung Yu
Yu-Liang Kuo
Li-Ching Chang
author_facet Ching-Wen Liu
Yu-Tse Wu
Kai-Jen Lin
Tsan-Jung Yu
Yu-Liang Kuo
Li-Ching Chang
author_sort Ching-Wen Liu
collection DOAJ
description 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.
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spelling doaj.art-b3a155e4bd204d449b6863ae9bafd7a02022-12-22T02:17:57ZengMDPI AGMolecules1420-30492016-06-0121671210.3390/molecules21060712molecules21060712A Hydrogel-Based Epirubicin Delivery System for Intravesical ChemotherapyChing-Wen Liu0Yu-Tse Wu1Kai-Jen Lin2Tsan-Jung Yu3Yu-Liang Kuo4Li-Ching Chang5School of Pharmacy, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 807, TaiwanSchool of Pharmacy, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 807, TaiwanDepartment of Pathology, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, TaiwanDepartment of Urology, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, TaiwanDepartment of Medical Imaging and Radiological Sciences, Chung Shan Medical University, No.110, Sec. 1, Jianguo North Rd., South District., Taichung 402, TaiwanDepartment of Occupational Therapy, I-Shou University, No.8, Yida Road, Yanchao District, Kaohsiung 824, TaiwanThis 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.http://www.mdpi.com/1420-3049/21/6/712epirubicinhydrogelintravesicalbladder cancer
spellingShingle Ching-Wen Liu
Yu-Tse Wu
Kai-Jen Lin
Tsan-Jung Yu
Yu-Liang Kuo
Li-Ching Chang
A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
Molecules
epirubicin
hydrogel
intravesical
bladder cancer
title A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
title_full A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
title_fullStr A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
title_full_unstemmed A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
title_short A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy
title_sort hydrogel based epirubicin delivery system for intravesical chemotherapy
topic epirubicin
hydrogel
intravesical
bladder cancer
url http://www.mdpi.com/1420-3049/21/6/712
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