Al-Hilal, Taslim A. Alam, Farzana Park, Jin Woo Kim, Kwangmeyung Kwon, Ick Chan Ryu, Gyu Ha Byun, Youngro 2024-01-20T08:03:58Z 2024-01-20T08:03:58Z 2021-09-05 2014-12-10 0168-3659 https://pubs.kist.re.kr/handle/201004/125999 Thrombogenesis is a major cause of morbidity and mortality in cancer patients. Prophylaxis with low-molecular-weight heparin (LMWH) is recommended for cancer patients, but requires non-parenteral delivery methods for long-term treatments. In this study, we sought to generate a new oligomeric-bile acid conjugate of LMWH that can be used for oral delivery. We first synthesized a tetramer of deoxycholic acid (tetraDOCA), which was site-specifically conjugated at the end saccharide of LMWH. When LMWH-tetraDOCA conjugate (LHe-tetraD) was orally administered at a dose of 5 mg/kg in ICR mice, the maximum anti-factor Xa level was increased up to 0.62 +/- 0.05 IU/mL without any evidence of liver toxicity, gastrointestinal damage, or thrombocytopenia. The cancer-associated thrombosis was induced in tumor-bearing mice by local heat application, and the fibrin deposition in tumors was evaluated. The oral administration of LHe-tetraD (either a single dose or multiple daily doses for up to 10 days) in mice substantially abolished the coagulation-dependent tropism of fibrinogen in the heated tumors and significantly decreased hemorrhage, compared to the mice treated with saline or subcutaneous injection of LMWH. Thus, the anticoagulation effect of oral LHe-tetraD invokes the benefits of oral delivery and promises to provide an effective and convenient treatment for cancer patients at risk of thrombosis. (C) 2014 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV MOLECULAR-WEIGHT HEPARIN BILE-ACID TRANSPORTERS VENOUS THROMBOEMBOLISM BLEEDING COMPLICATIONS MALIGNANT GLIOMAS DRUG-DELIVERY CHEMOTHERAPY COAGULATION FIBRINOGEN INSIGHTS Prevention effect of orally active heparin conjugate on cancer-associated thrombosis Article 10.1016/j.jconrel.2014.05.027 1 JOURNAL OF CONTROLLED RELEASE, v.195, pp.155 - 161 JOURNAL OF CONTROLLED RELEASE 195 155 161 scie scopus 000344230500019 2-s2.0-84908590374 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article; Proceedings Paper MOLECULAR-WEIGHT HEPARIN BILE-ACID TRANSPORTERS VENOUS THROMBOEMBOLISM BLEEDING COMPLICATIONS MALIGNANT GLIOMAS DRUG-DELIVERY CHEMOTHERAPY COAGULATION FIBRINOGEN INSIGHTS Heparin conjugate Oral delivery Anticoagulants Cancer-associated thrombosis