Use of avidin/biotin-lipo some system for enhanced peritoneal drug delivery in an ovarian cancer model

The goal of this study was to determine the distribution of the avidin/biotin-liposome system in an ovarian cancer xenograft model. Optimal avidin/biotin-liposome injection sequence with enhanced liposome accumulation to the peritoneum was determined. Two weeks after NIH:OVCAR-3 cell inoculation, rats were divided into three groups. Group 1 (B-A) (n = 4), received an intraperitoneal injection of Tc-99m-blue-biotin-liposomes 30 min before an intraperitoneal injection of avidin. Group 2 (A-B) (n = 4), received an intraperitoneal injection of avidin 30 min before an intraperitoneal injection of Tc-99m-blue-biotin-liposomes. Group 3 (A-B 2h) (n = 5), received an intraperitoneal injection of avidin 2 h before an intraperitoneal injection of Tc-99m-blue-biotin-liposomes. Three additional non-tumor nude rats served as controls in each group, and were subjected to the same injection sequences. Scintigraphic imaging commenced at various times post Tc-99m-blue-biotin-liposome injection. After imaging, rats were euthanized at 23 h post-liposome injection for tissue biodistribution. Images showed no apparent difference in liposome distribution between control and tumor animals. Regional uptake analysis. at 4 h for tumor rats showed significantly higher lymphatic channel uptake in the A-B 2h group (p < 0.05) and a trend of increased peritonea] uptake in A-B group. By 22 h, peritoneal and lymphatic channel uptake was similar for all groups. At necropsy, most activity was found in blue-stained omentum, diaphragm, mediastinal and abdominal nodes. Bowel activity was minimal. These results correlate with previous normal rat studies, and demonstrate potential use of this avidin/biotin-liposome system for prolonging drug delivery to the peritoneal cavity and associating lymph nodes in this ovarian cancer xenograft model. (c) 2007 Elsevier B.V. All rights reserved.