Tumor Drug Distribution after Local Drug Delivery by Hyperthermia, In Vivo

Tumor drug distribution and concentration are important factors for effective tumor treatment. A promising method to enhance the distribution and the concentration of the drug in the tumor is to encapsulate the drug in a temperature sensitive liposome. The aim of this study was to investigate the tumor drug distribution after treatment with various injected doses of different liposomal formulations of doxorubicin, ThermoDox (temperature sensitive liposomes) and DOXIL (non-temperature sensitive liposomes), and free doxorubicin at macroscopic and microscopic levels. Only ThermoDox treatment was combined with hyperthermia. Experiments were performed in mice bearing a human fibrosarcoma. At low and intermediate doses, the largest growth delay was obtained with ThermoDox, and at the largest dose, the largest growth delay was obtained with DOXIL. On histology, tumor areas with increased doxorubicin concentration correlated with decreased cell proliferation, and substantial variations in doxorubicin heterogeneity were observed. ThermoDox treatment resulted in higher tissue drug levels than DOXIL and free doxorubicin for the same dose. A relation with the distance to the vasculature was shown, but vessel perfusion was not always sufficient to determine doxorubicin delivery. Our results indicate that tumor drug distribution is an important factor for effective tumor treatment and that its dependence on delivery formulation merits further systemic investigation.

Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis

The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5 mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6 ± 3.2 cm3) compared with the DEM-BLAND group (8.9 ± 5.4 cm3) (p = 0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38% ± 17%) compared with the DEM-BLAND group (56% ± 20%) (p = 0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094 ± 0.852 mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0 µM up to a distance of 1.4 mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1 week.

Preparation and Application of a Nano α-Fe2O3/SAPO-34 Photocatalyst for Removal of the Anti-cancer Drug Doxorubicin using the Taguchi Approach

The synthesis of α-Fe2O3/SAPO-34 nano photocatalyst was the first step of this study. The α-Fe2O3 nanocatalyst was synthesized applying forced hydrolysis and reflux condensation followed by solid-state dispersion that was used for supporting α-Fe2O3 on SAPO-34. The next step was a characterization of the catalyst that was performed using X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR). Then, for optimizing the operational parameters in Doxorubicin’s degradation process the effect of Doxorubicin concentration, the amount of α-Fe2O3/SAPO-34 nano photocatalyst, the pH, and H2O2 concentration was studied via the Taguchi method. The AL9 orthogonal array was adjusted and nine crucial runs were conducted. For calculating Signal/Noise ratio, each run was repeated three times. As the results showed, the concentration of Doxorubicin is the most effective parameter. Optimized conditions for removing the anti-cancer drug (based on Signal/Noise ratio) were Doxorubicin concentration (20 ppm), H2O2 concentration (3 mol/L), catalyst amount (50 mg/L) and pH = 8.