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Differential Adhesion of Normal and Inflamed Rat Colonic Mucosa by Charged Liposomes

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Abstract

Purpose. To study the adhesion properties of charged liposomes to the healthy and inflamed (colitis-induced) rat intestinal epithelium.

Methods. Neutral, positively charged, and negatively charged liposomes were prepared and tagged. The cationic or anionic liposomes contained increasing amounts (13, 22, or 36 mol%) of either the cationic lipid dimethyl-dioctadecylammoniumbromide (DODAB) or the anionic lipid 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DSPG). Colitis was induced in rats by DNBS. Adhesion of the various types of liposomes was assessed in rat colon sacs. The effects of charge type, charge density (mol%), liposome size, and incubation time on the adhesion of the liposomes were compared in the inflamed and healthy epithelial tissues.

Results. Three times as many cationic liposomes adhered to the healthy colonic mucosa than neutral or anionic liposomes. However, anionic liposome adherence to the inflamed colonic mucosa was 2-fold that of either neutral or cationic liposomes (a finding that was verified by charged-dyes studies). Adherence was directly correlated with charge density. An inverse correlation was identified between cationic liposome size and healthy tissue adherence in short incubation periods. The adherence of cationic liposomes, which was also found to be time-dependent, decreased in healthy mucosa in the presence of high concentrations of aqueous Mg 2+ rinse.

Conclusions. Anionic liposomes could be useful for the topical delivery of anti-inflammatory drugs in inflammatory bowel disease therapy.

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Authors and Affiliations

  1. Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem, 91120, Israel

    Tareq Taha Jubeh

  2. Laboratory of Membrane and Liposome Research, The Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel

    Yechezkel Barenholz

  3. Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem, 91120, Israel

    Abraham Rubinstein

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  1. Tareq Taha Jubeh
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  2. Yechezkel Barenholz
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  3. Abraham Rubinstein
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Correspondence to Abraham Rubinstein.

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Jubeh, T.T., Barenholz, Y. & Rubinstein, A. Differential Adhesion of Normal and Inflamed Rat Colonic Mucosa by Charged Liposomes. Pharm Res 21, 447–453 (2004). https://doi.org/10.1023/B:PHAM.0000019298.29561.cd

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