被撤回的出版物: Evaluation of the oral bioavailability of low molecular weight heparin formulated with glycyrrhetinic acid as permeation enhancer (Retracted article. See vol. 69, pg. 535, 2008)

Low molecular weight heparin (LMWH) is the agent of choice for anticoagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, its therapeutic use is limited due to poor oral bioavailability. The aim of this study was to investigate the oral delivery of LMWH, ardeparin formulated with 18-beta glycyrrhetinic acid (GA), as an alternative to currently used subcutaneous (sc) delivery. Drug transport through Caco-2 cell monolayers was monitored in the presence and absence of CA by scintillation counting and transepithelial electrical resistance. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. The absorption of ardeparin after oral administration in rats was measured by an anti-factor Xa assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. Higher ardeparin permeability (similar to 7-fold) compared to control was observed in the presence of 0.02% GA. Regional permeability studies indicated predominant absorption in the duodenal segment. Cell viability studies showed no significant cytotoxicity below 0.01% GA. Ardeparin oral bioavailability was significantly increased (Frelative/s.c. = 13.3%) without causing any damage to the intestinal tissues. CA enhanced the oral absorption of ardeparin both in vitro and in vivo. The oral formulation of ardeparin with CA could be absorbed in the intestine. These results suggest that CA may be used as an absorption enhancer for the oral delivery of LMWH.