The need for improved specificity in the local treatment of inflammatory bowel diseases (IBD) led us to use negatively charged liposomes to target the inflamed colonic epithelium. The purpose of the present study was to elucidate the cause for our previous observations that such liposomes accumulate, preferentially, in the inflamed mucosa of rats that were induced with experimental colitis, following luminal administration. Protein analysis (tandem mass spectrometry, verified by Western blot) of inflamed mucosal specimens, extracted at pH 3, 5 and 7, revealed an increased expression of transferrin (TF) at pH 3. Histological examination indicated that the TF was located at the luminal side of the inflamed epithelium. Negatively charged (but not neutral) liposomes adhered to both commercial and mucosal TF at low pH, but not at neutral pH. Moreover, preincubation of negatively charged liposomes with TF profoundly attenuated their adherence to the inflamed mucosa of the rat colon. It is concluded that, at a low pH, typical of the colon lumen in ulcerative colitis, TF mediates specific mucoadhesion of negatively charged liposomes to the inflamed mucosa. This observation could be useful in the rational design of specific drug vehicles aimed at IBD therapy after luminal administration.
Tirosh B, Khatib N, Barenholz Y, Nissan A, Rubinstein A.
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel, Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel, Laboratory of Membrane and Liposome Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel, and Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, P.O. Box 24035, Jerusalem 91240, Israel