Abstract
1596
Objectives The goal was to investigate the in vivo behavior of 99mTc-labeled acid-stable liposomes following oral administration in rats using nuclear imaging, blood sampling and biodistribution.
Methods Groups investigated included 1) 99mTc-G4 (distearoyl phosphatidylcholine (DSPC): cholesterol:asparagine-lipid; 55/40/5), 2) 99mTc-G7(DSPC/Chol ;60/40), 3) 99mTc-pegylated liposome doxorubicin (Doxil®), and 4) 99mTc-BMEDA as control (n=5 in each group). Nude rats (~210 g) were administered 3.5 ml of 99mTc-liposomes (9mM) or 99mTc-BMEDA by gavage. Images were acquired at various time points. Also, blood samples (200 µl) were collected through tail vein at 0.08, 2, 4 and 20 h before biodistribution was performed. Regions-of-interest (ROI) of stomach and intestine for each animal were drawn and corrected with total radioactivity administered. The 99mTc-activity in blood and organs were measured by gamma counter.
Results There were 5+/-4.3%, 3+/-4.6%, 8+/-11.2% and 35+/-21.7%ID in stomach, and 75+/-8.5%, 81+/-6.1%,78+/-17.6%, and 53+/-24.75%ID in intestine for the G4, G7, Doxil®, and 99mTc-BMEDA groups, respectively, in 2 h images. 99mTc-bioavailability of Doxil and G4 (~0.01% ID/g) were higher than G7 (~0.005% ID/g) at 2 h and 4 h (p <0.05). The ROIs of intestines have positive correlations with 99mTc-activity in blood samples for Doxil( R2>0.6 at 2h), G7(R2>0.9 at 0.08h) and 99mTc-BMEDA(R2>0.9 at 2h). But, there was no significant difference between liposomal and control groups in biodistribution.
Conclusions Use of 99mTc-imaging technique can monitor oral liposomal behavior in gastrointestinal environments. Liposomes are stable in acidic stomach region, especially, Doxil and asparagine-derived liposomes; which protect against intestinal enzymes and increase the permeability of liposomes in intestinal cells.
Research Support Partly supported by San Antonio Life Science Institute