Evaluation of pharmacokinetics of 111In-labeled VNB-PEGylated liposomes after intraperitoneal and intravenous administration in a tumor/ascites mouse model.
Nanoliposomes are important drug carriers that can passively target tumor sites by the enhanced permeability and retention (EPR) effect in neoplasm lesions. This study evaluated the biodistribution and pharmacokinetics of 111In-labeled vinorelbine (VNB)-encapsulated PEGylated liposomes (IVNBPL) after intraperitoneal (i.p.) and intravenous (i.v.) administration in a C26/tk-luc colon carcinoma ascites mouse model. IVNBPL was prepared by labeling VNB-encapsulated PEGylated liposomes with 111In-oxine. BALB/c mice were i.p. inoculated with 2 x 10(5) C26/tk-luc cells in 500 muL of phosphate-buffered saline. Peritoneal tumor lesions were confirmed by 124I-FIAU/micro-PET (positron emission tomography) and bioluminescence imaging. Ascites production was examined by ultrasound imaging on day 10 after tumor cell inoculation. The pharmacokinetics and biodistribution studies of IVNBPL in a tumor/ascites mouse model were conducted. The labeling efficiency was more than 90%. The in vitro stability in human plasma at 37 degrees C for 72 hours was 83% +/- 3.5%. For i.p. administration, the areas under curves (AUCs) of ascites and tumor were 6.78- and 1.70-fold higher, whereas the AUCs of normal tissues were lower than those via the i.v. route. This study demonstrates that i.p. administration is a better approach than i.v. injection for IVNBPL, when applied to the treatment of i.p. malignant disease in a tumor/ascites mouse model.
Lin
Yi-Yu
YY
Biomedical Imaging and Radiological Sciences, National Yang-Ming University , Taipei, Taiwan, Republic of China.
Li
Jia-Je
JJ
Chang
Chih-Hsien
CH
Lu
Yi-Ching
YC
Hwang
Jeng-Jong
JJ
Tseng
Yun-Long
YL
Lin
Wuu-Jyh
WJ
Ting
Gann
G
Wang
Hsin-Ell
HE
D000818:Animals; D001201:Ascites / Q000000981:diagnostic imaging / Q000378:metabolism; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D014018:Tissue Distribution; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine
D007205:Indium Radioisotopes; D008081:Liposomes; D011092:Polyethylene Glycols; D014747:Vinblastine; D000077235:Vinorelbine