Intratumoral Injection of Holmium-Chitosan Complex in Prostate Cancer / 대한비뇨기과학회지

PURPOSE: The aim of this study was to pathologically evaluate the therapeutic and toxic effects of the 166Ho-chitosan complex(166HC) on prostatic cancer. MATERIALS AND METHODS: The DU-145 cell line was subcutaneously heterotransplanted into 30 nude mice, resulting in 24 prostatic cancers. The 24 nude mice with prostatic cancer were divided into four groups. Group I(n=6) received 0.5ml normal saline, group II(n=6) 0.5ml chitosan, group III(n=6) 370 MBq of 166HC and group IV(n=6) 740 MBq of 166HC per 1cm3, intratumorally. The tumor sizes were measured at 1 and 2 weeks after injection. The 24 mice were sacrificed and pathological examination performed: Haematoxylin & Eosin(H & E) staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling(TUNEL) staining. RESULTS: Two weeks after injection of 166HC, the tumor volumes in groups III and IV were smaller than those in groups I and II(p<0.05). H & E staining of the tumors showed wide central necrosis in groups III and IV, but not in groups I and II. TUNEL staining showed false positive reactions along the peripheral margins in all groups. No toxic changes were found in the liver, kidney, peripheral blood and bone marrow. CONCLUSIONS: An intratumoral injection of 166HC appears to be a new, safe and promising alternative radiotherapeutic modality for the local control of prostatic cancer, with minimized toxicities as the administered 166HC is retained at the injection site.

Efficacy of Paclitaxel-Loaded Bioadhesive Drug Deliver System Based on Glyceryl Monooleate Nanoparticle in an Orthotopic Murine Bladder Cancer Model / 대한비뇨기과학회지

Purpose: The purpose of this study was to evaluate the efficacy of paclitaxel-loaded glyceryl monooleate (GMO) in the intravesical treatment of superficial transitional cell carcinomas of the bladder by enhancing the bioadhesiveness and bioavailability. Materials and Methods: A mucoadhesive oily paclitaxel formulation was prepared using GMO, tricaprylin, Tween(8) 80 and paclitaxel. The bioactivity of the GMO/paclitaxel formulation was confirmed by assessing its cytotoxicity on MBT-2, a bladder cancer cell line. An in vivo study was performed in C3H2 mice after induction of bladder cancer by an intravesical bladder tumor implantation. The efficacy of the intravesical administration of the GMO/paclitaxel was assessed by the histology and bladder weight. Results: The average particle size of the GMO/paclitaxel was 600nm. Only 2.6% of the MBT-2 cells were viable after 24 hours of treatment with GMO/paclitaxel at a paclitaxel concentration of 10microgram/ml. In the orthotopic bladder cancer model the tumor incidence rate was significantly decreased by intravesical administration of the GMO/paclitaxel compared to the controls. The average bladder weight of the GMO/paclitaxel group was significantly lower than that of controls. No toxicity was observed in either of the groups. Conclusions: Intravesical administration of the GMO/paclitaxel formulation had an inhibitory effect on the bladder tumor in an orthotopic bladder cancer model. This formulation may be a promising approach for intravesical chemotherapy of superficial bladder cancer.

Bioadhesive Drug Delivery System for the Intravesical Administration of Paclitaxel in Rabbits / 대한비뇨기과학회지

PURPOSE: Many reports have shown that the efficacy of intravesical therapy for bladder cancer is, in part, limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the delivery and penetration of paclitaxel into the bladder of rabbits, when given as an intravesical dose. MATERIALS AND METHODS: The urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120min with paclitaxel (500g/20ml) by an intravesical instillation. Two formulation of GMO/paclitaxel were evaluated, according to the proportion of water, 15% and 30%, with Taxol was used as a control. The animals were observed for clinical signs of toxicity, and necropsy performed. RESULTS: At 120min post-instillation, the bladders were emptied and excised. The urine paclitaxel concentrations were decreased by 39.6 and 41.2% in the two experimental groups, and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in the two experimental groups, respectively, but by only 11% in the control group. The concentration then declined exponentially in the underlying capillary perfused tissues, reaching equilibrium at a depth of 1,400-1,700um. The plasma concentrations were extremely low compared with those in the urine and bladder tissues, and were not associated with clinical toxicity. CONCLUSIONS: These results indicate that GMO improves the delivery of paclitaxel and increases the concentration in the bladder tissue. These results suggest that the intravesical delivery of GMO/paclitaxel/water provide a significant bladder tissue targeting advantage, and that paclitaxel represents a viable candidate drug for intravesical bladder cancer therapy.