کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2505855 1557502 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Doubly radiolabeled liposomes for pretargeted radioimmunotherapy
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Doubly radiolabeled liposomes for pretargeted radioimmunotherapy
چکیده انگلیسی

The aim of this study was to design liposomes as radioactivity carriers for pretargeted radioimmunotherapy with favorable pharmacokinetic parameters. To monitor the liposomes integrity in vivo, their surface was radiolabeled with indium-111 bound to DTPA-derivatized phosphatidylethanolamine (DSPE-DTPA) and the aqueous phase was labeled by using an original active loading technique of radioiodinated Bolton–Hunter reagent (BH) that reacts with pre-encapsulated arginine to form a positively charged conjugate (125I-BH-arginine). Different formulations of doubly radiolabeled liposomes were tested in vitro and in vivo to evaluate radiolabeling stability, integrity of the vesicles and their pharmacokinetics.Radiolabeling yields were high (surface >75%, encapsulation >60%) and stable (>85% after 24 h in serum 37 °C). In vivo, the pharmacokinetic behavior of doubly radiolabeled liposomes was strongly dependant on the formulation. Blood clearance of PEGylated liposomes (DSPC/Chol/DSPE-DTPA/DSPE-PEG5%) was 0.15 mL/h compared to a conventional formulation (DSPC/Chol/DSPE-DTPA: clearance 1.44 mL/h). Non-encapsulated BH-arginine conjugate was quickly eliminated in urine (clearance 6.04 mL/h). Blood kinetics of the two radionuclides were similar and radiochromatographic profiles of mice serum confirmed the integrity of circulating liposomes. The significant reduction of activity uptake in organs after liposome catabolism (liver and spleen), achieved by the rapid renal elimination of 125I-BH-arginine, should bring significant improvements for targeted radionuclide therapy with sterically-stabilized liposomes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 344, Issues 1–2, 1 November 2007, Pages 110–117
نویسندگان
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