Abstract
Intravesical administration of chemotherapeutic agents can enhance drug accumulation in tumors and reduce systemic side effects. Nanocarriers were developed for intravesical administration and exploit the permeation enhancement effect. In vitro permeation evaluation, the drug transdermal amount and accumulation amounts in the tissue of gemcitabine-loaded nanocarriers through biological membrane significantly increased about 14.8~33.0-fold and 1.5~14.1-fold respectively, when compared to a control group of 1% gemcitabine saline solution. In in vivo intravesical administration, the drug accumulation amount in bladder tissue of nanocarrier of 75.2 ± 5.4 μg was revealed as being comparably higher than that of the control group of 44.8 ± 6.4 μg. In confocal laser scanning microscopy imagery, the penetration depth of fluorescent dyes-rhodamine was increased from 80 μm up to 120 μm when a nanocarrier was used. This result implies that the nanocarrier is a promising drug delivery agent for intravesical administration.
Highlights
Bladder cancer is a common genitourinary malignancy involving the urinary system, and is commonly divided into non-muscle invasive or superficial bladder cancer and muscle-invasive bladder cancer where the cancer extends into the underlying smooth muscle [1,2]
The treatment of superficial bladder cancer involves transurethral resection of visible tumors followed by chemotherapy for the prevention of recurrent tumors
The gel-based nanocarriers were designed for intravesical administration
Summary
Bladder cancer is a common genitourinary malignancy involving the urinary system, and is commonly divided into non-muscle invasive or superficial bladder cancer (approximately 70%) and muscle-invasive bladder cancer where the cancer extends into the underlying smooth muscle [1,2]. The intravesical chemotherapy agent provides high drug concentrations at the disease site, and minimum systemic side effects due to the theoretically negligible systemic uptake. Microemulsion is a useful nanocarrier in the pharmaceutical field, because its composition (an aqueous phase, oil phase, surfactant and often cosurfactant) is simple, and easy to prepare. Microemulsion incorporated hydrophilic polymer to form gel-based microemulsion, which could increase the retention time of formulations on the administration site, result in increased therapeutic efficacy. The gel-based nanocarriers were designed for intravesical administration. The response surface methodology (RSM) with a constrained mixture design was used to realize the effect of surfactant and cosurfactant of microemulsion and we obtained an optimal formulation
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