Accumulation of PEG-liposomes in the Inflamed Colon of Rats: Potential for Therapeutic and Diagnostic Targeting of Inflammatory Bowel Diseases

Abstract

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.

Radiosynthesis and in vivo evaluation of a F‐18‐labeled pancreatic islet amyloid inhibitor

“…The total blood, muscle, and bone mass were estimated as 5.7, 40 and 10% of the total body weight, respectively. 36 The weight of stomach and intestines included their contents.…”

Alternative Drug Delivery Approaches for the Therapy of Inflammatory Bowel Disease

“…Intravenously administered liposomes showed an increased uptake in the inflamed colonic tissue owing the endothelium fenestration in the inflamed area and were able to visualize colitic lesions 93, 94. In consequence, liposomes have been developed as drug targeting agents for the treatment of IBD 95. Injected PEG‐liposomes preferentially accumulated in the inflamed tissue of colitis rats (around 13%), against 0.1% in the normal region of the control group.…”

Intravenous technetium‐99m labelled PEG‐liposomes in horses: A safety and biodistribution study

“…Due to their long circulating characteristics and ability to extravasate, radiolabelled PEG-liposomes are useful for scintigraphic imaging. They have been validated for imaging infections (Goins et al 1993;Awasthi et al 1998;Dams et al 2000), arthritis (Boerman et al 1997), neoplasia (Arulsudar et al 2004) and colitis (Dams et al 1998;Awasthi et al 2002). In multiple animal models and man they are considered superior to radiolabelled leucocytes and IgG (Dams et al 1998).…”