title: Evaluation of pharmacokinetics of 111In-labeled VNB-PEGylated liposomes after intraperitoneal and intravenous administration in a tumor/ascites mouse model.
abstract: 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.
authors.affiliation: Biomedical Imaging and Radiological Sciences, National Yang-Ming University , Taipei, Taiwan, Republic of China.
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Jia-Je
authors.initials: JJ
authors.lastname: Li
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lu
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Tseng
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Gann
authors.initials: G
authors.lastname: Ting
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
mesh_terms: 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
chemical_list: D007205:Indium Radioisotopes; D008081:Liposomes; D011092:Polyethylene Glycols; D014747:Vinblastine; D000077235:Vinorelbine