Hyperbranched polyglycerol-docetaxel treatments for bladder cancer and the characterization of treated bladder tissue using MALDI-MS imaging

Introduction In North America, bladder cancer is the 4th most common cancer in men and the 9th in women and is reported to have the highest lifetime cost per patient of all cancers. Furthermore, innovations in the treatment... [ view full abstract ]

Introduction

In North America, bladder cancer is the 4th most common cancer in men and the 9th in women and is reported to have the highest lifetime cost per patient of all cancers. Furthermore, innovations in the treatment of bladder cancer have been slow to develop and there remain significant unmet medical needs. The use of mucoadhesive nanoparticles based on amine-modified hyperbranched polyglycerols (HPGs) as vehicles for delivery of the taxane drug docetaxel (DTX), including drug uptake, efficacy, safety and pharmacokinetics, has been the subject of our recent research. In this context, the aim of the study reported here was to demonstrate that DTX could be visualized and quantified in bladder tissue by means of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. The objectives of the research were to compare HPG-DTX formulations with Taxotere®, an existing commercial treatment, when applied to ex vivo pig bladder samples, which would then be sectioned and examined using MALDI-MS imaging. Results in terms of drug quantitation and penetration in the tissue could then be compared with results obtained using alternative analytical methods.

Methods

Freshly obtained pig bladders were transferred to pH 7.4 buffer and cut into 1 x 1 cm samples. These samples, urothelium side upwards, were placed in Franz diffusion cells and the donor compartments filled with 300 μls of either an HPG-DTX formulation or a Taxotere® formulation. Following incubation at 37oC, the samples were removed from the cells and frozen before cutting into thin sections at 90o to the urothelium surface. The surfaces of these sections were then examined using MALDI-MS imaging and compared with treated and untreated controls.

Results

The distribution and concentrations of DTX in pig bladder tissue determined using MALDI-MS imaging, as illustrated in the Figure, were comparable with results obtained previously using an established radiolabeled drug method and confirmed the higher loading of DTX in bladder tissue when using an HPG formulation.

Conclusions

The MALDI-MS imaging method provides a convenient means of visualizing DTX in treated bladder tissue and is a potentially useful alternative to the use of radiolabeled drug or other methods for drug quantitation.