TY - JOUR
T1 - Use of avidin/biotin-liposome system for enhanced peritoneal drug delivery in an ovarian cancer model
AU - Zavaleta, Cristina L.
AU - Phillips, William T.
AU - Soundararajan, Anuradha
AU - Goins, Beth A.
PY - 2007/6/7
Y1 - 2007/6/7
N2 - 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 99mTc-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 99mTc-blue-biotin-liposomes. Group 3 (A-B 2h) (n = 5), received an intraperitoneal injection of avidin 2 h before an intraperitoneal injection of 99mTc-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 99mTc-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 peritoneal 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.
AB - 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 99mTc-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 99mTc-blue-biotin-liposomes. Group 3 (A-B 2h) (n = 5), received an intraperitoneal injection of avidin 2 h before an intraperitoneal injection of 99mTc-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 99mTc-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 peritoneal 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.
KW - Avidin-biotin system
KW - Drug delivery
KW - Liposomes
KW - Nude rats
KW - Ovarian cancer
KW - Small animal imaging
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UR - http://www.scopus.com/inward/citedby.url?scp=34248582837&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2007.01.010
DO - 10.1016/j.ijpharm.2007.01.010
M3 - Article
C2 - 17276633
AN - SCOPUS:34248582837
VL - 337
SP - 316
EP - 328
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -