A SIMPLE METHOD FOR RADIOLABELING PH SENSITIVE LIPOSOMES.

GABRIELA NAVARRO ,VICTORIA TRINDADE ,PABLO CABRAL ,MARCELO FERNÁNDEZ ,PAOLA AUDICIO ,EMILIA REZZANO ,ANTONIO MALANGA ,OMAR MARTIN ,MARÍA JOSÉ MORILLA ,EDER ROMERO ,HENIA BALTER ,EDUARDO SAVIO

Amsterdam

Congreso; Pharmaceutical Science World Congress; 2007

International Pharmaceutical Federation

Upon acidification, the bilayer of pH-sensitive liposomes fuse with endo-lysosomal membranes, to subsequently release their aqueous content to the cytoplasm. This triggered transition makes them efficient tools for intracellular, selective and massive delivery of drugs. However, there are still few data on their plasma stability and biodistribution. Because of that, the aim of this work was to follow the biodistribution of pH-sensitive liposomes labeled with 99mTc-N 2,6 diisopropilphenilcarbamoilmetil iminodiacetic acid (DISIDA). Radiolabeling of pH-sensitive liposomes composed of dioleoyl-phosphatidylethanolamine: cholesteryl hemisuccinate (6:4 mol/mol) prepared by extrusion, was done by the simple addition of 99mTc- DISIDA to a liposomal aqueous dispersion. Separation of free label from liposomes and labeling yield were determined by gel filtration in PD10 column and liposomal size distribution by laser light diffraction. Label stability was determined by dialysis using a 14 kDa membrane. Biodistribution upon endovenous administration of single bolus of liposomal suspension was followed in CD1 mice after 5, 15 and 30 min. Our results showed that pH-sensitive liposomes between 40 and 102 nm (99.6%) with >99% of labeling yield were obtained. The label remained associated to the liposomes at least for 2 h where liposomes showed 95% of 99mTc-DISIDA retained. On the other hand, as expected for these nanocarriers, liposomal biodistribution showed accumulation in liver, spleen, and lungs. This study shows that the incorporation of 99mTc-DISIDA could be used as a fast, simple, stable and efficient method for labeling pH-sensitive liposomes.