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 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.
School of Pharmacy, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 807, Taiwan. fruit0227@hotmail.com.
Ching-Wen
CW
Liu
School of Pharmacy, Kaohsiung Medical University, No.100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung 807, Taiwan. ytwu@kmu.edu.tw.
Yu-Tse
YT
Wu
Department of Pathology, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, Taiwan. ed102328@edah.org.tw.
Kai-Jen
KJ
Lin
Department of Urology, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, Taiwan. ed100622@edah.org.tw.
Tsan-Jung
TJ
Yu
Department of Medical Imaging and Radiological Sciences, Chung Shan Medical University, No.110, Sec. 1, Jianguo North Rd., South District., Taichung 402, Taiwan. yuliangkuo622@gmail.com.
Yu-Liang
YL
Kuo
Department of Occupational Therapy, I-Shou University, No.8, Yida Road, Yanchao District, Kaohsiung 824, Taiwan. changlc@isu.edu.tw.|Department of Pharmacy, E-Da Hospital, I-Shou University, No.1, Yida Road, Yanchao District, Kaohsiung 824, Taiwan. changlc@isu.edu.tw.
Li-Ching
LC
Chang
D000283:Administration, Intravesical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015251:Epirubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D010539:Permeability; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D015251:Epirubicin; D053148:Caspase 3
bladder cancer; epirubicin; hydrogel; intravesical