Accumulation of PEG-liposomes in the inflamed colon of rats: potential for therapeutic and diagnostic targeting of inflammatory bowel diseases.

Therapeutic intervention in inflammatory bowel diseases (IBDs) is often associated with severe toxicity related to the nonspecific and ubiquitous interaction of drugs with the organs and tissues. In order to prevent side effects from aggressive and prolonged treatment with glucocorticoids and immunosuppressive agents, preferential accumulation of these potent drugs in diseased tissue is desired. In this work, we report that liposomes show a remarkable tendency to accumulate in inflamed colon of rats with experimental colitis. The disposition of liposomes was monitored by labeling them with Tc-99m followed by gamma camera imaging, and determining biodistribution of radioactivity in various organs. The images showed distinct accumulation of radioactivity in the colon of rats with colitis, while the abdomen of normal rats was conspicuously free of any visible radioactivity. Although images acquired 4 h after Tc-99m-liposome injection were clear enough for diagnostic indication, the real potential of liposomes for drug delivery was evident in 24 h images where the major organs of liposome accumulation were dwarfed by intense colon activity in animals with colitis. On necropsy, 13.5% +/- 5.48 of the activity accumulated in the inflamed colon as compared to only 0.1% in the normal colon, giving a target-to-nontarget ratio of 135. The blood borne radioactivity was 9% +/- 2.12 (colitis) and 25.7% +/- 4.27 (normal), indicating that the decrease in circulating liposomes is associated with an increase in liposome accumulation in the inflammatory site. The other two major organs that accumulated liposomes were spleen (10.7% normal vs. 11% colitis) and liver (8% normal vs. 10.1% colitis). In conclusion, this study demonstrates the innate propensity of liposomes to accumulate in the sites of inflammation and potential of liposomes loaded with therapeutic drugs or diagnostic agents for targeting colitis.