Bita Moazed1, Linda M Hiebert. 1. Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan, S7N 5B4, Canada.
Abstract
PURPOSE: Movement of unfractionated (UFH) and low molecular weight heparins (LMWHs) through gastric mucosa was compared to determine effect of molecular weight on absorption. METHODS: Rat gastric mucosa, mounted in an Ussing chamber, was bathed in oxygenated Kreb's buffer, containing mannitol on the mucosal (lumen) at pH 7.4 or 4, and glucose on the serosal side (circulation) at pH 7.4. Heparins (10 mg/ml) were added to the mucosal side. Potential difference (PD), resistance, and short circuit current (Isc), were determined. Buffers and tissues were extracted to measure heparin by gel electrophoresis. RESULTS: PD increased on heparin addition and following a lag period, that was longer for UFH at pH 7.4 and LMWHs at pH 4.0, returned to baseline. Isc increased slightly for UFH at pH 4.0 but significantly for LMWHs at pH 7.4. More UFH or LMWHs were recovered from serosal buffers at pH 4.0 and pH 7.4 respectively. Results suggest UFH and LMWHs cross gastric mucosa faster, and active transport is involved, at pH 4.0 and pH 7.4, respectively. CONCLUSIONS: Decreasing heparin size, increases movement through gastric mucosa at mucosal buffer pH 7.4 but not pH 4.0. The stomach environment may favor UFH absorption while the intestine environment favors LMWH absorption.
PURPOSE: Movement of unfractionated (UFH) and low molecular weight heparins (LMWHs) through gastric mucosa was compared to determine effect of molecular weight on absorption. METHODS:Rat gastric mucosa, mounted in an Ussing chamber, was bathed in oxygenated Kreb's buffer, containing mannitol on the mucosal (lumen) at pH 7.4 or 4, and glucose on the serosal side (circulation) at pH 7.4. Heparins (10 mg/ml) were added to the mucosal side. Potential difference (PD), resistance, and short circuit current (Isc), were determined. Buffers and tissues were extracted to measure heparin by gel electrophoresis. RESULTS:PD increased on heparin addition and following a lag period, that was longer for UFH at pH 7.4 and LMWHs at pH 4.0, returned to baseline. Isc increased slightly for UFH at pH 4.0 but significantly for LMWHs at pH 7.4. More UFH or LMWHs were recovered from serosal buffers at pH 4.0 and pH 7.4 respectively. Results suggest UFH and LMWHscross gastric mucosa faster, and active transport is involved, at pH 4.0 and pH 7.4, respectively. CONCLUSIONS: Decreasing heparin size, increases movement through gastric mucosa at mucosal buffer pH 7.4 but not pH 4.0. The stomach environment may favor UFH absorption while the intestine environment favors LMWH absorption.
Authors: Linda M Hiebert; Sandra M Wice; Tidly Ping; Ronald E Hileman; Tfilay Polat; Robert J Linhardt Journal: Pharm Res Date: 2002-06 Impact factor: 4.200
Authors: Alyaa Ramadan; Frederic Lagarce; Anne Tessier-Marteau; Olivier Thomas; Pierre Legras; Laurent Macchi; Patrick Saulnier; Jean Pierre Benoit Journal: Int J Nanomedicine Date: 2011-11-21