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.
Highlights
The standard-of-care therapy for non-muscle-invading bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT) followed immediately by a single intravesical dose of a chemotherapeutic agent or immunotherapeutic agent (e.g., BCG) to reduce recurrence and progression to a muscle-invasive disease [1]
Molecules 2016, 21, 712 therapy has advantages in allowing more targeted delivery of therapeutic agents to tumor cells located in the bladder epithelium and in reducing the side effects associated with systemic drug absorption
Pro- and cleaved-caspase-3 proteins were measured by western blotting to assess rates Figure 3D shows that epirubicin-loaded hydrogel (EPI-H) treatment caused a reduction in pro-caspase-3 levels and a concomitant increase in levels of cleaved-caspase-3 in Ay-27 cells
Summary
The standard-of-care therapy for non-muscle-invading bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT) followed immediately by a single intravesical dose of a chemotherapeutic agent (e.g., epirubicin) or immunotherapeutic agent (e.g., BCG) to reduce recurrence and progression to a muscle-invasive disease [1]. Molecules 2016, 21, 712 therapy has advantages in allowing more targeted delivery of therapeutic agents to tumor cells located in the bladder epithelium and in reducing the side effects associated with systemic drug absorption. Overall, this enables a broader therapeutic window. The first hurdle is limited dwell time of a drug in the bladder (2 h) due to washout during voiding. The second hurdle is the limited uptake of drug into the urothelial cells (normal or malignant) due to the unique permeability barrier properties of the urothelium [3]
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