title: A model ternary heparin conjugate by direct covalent bond strategy applied to drug delivery system.
abstract: A model ternary heparin conjugate by direct covalent bond strategy has been developed, in which modified heparin using active mix anhydride as intermediate conjugates with model drug molecule and model specific ligand, respectively. Designed ester bonds between model drug and heparin facilitate hydrolysis kinetics research. The strategy can be extended to design and synthesize a targeted drug delivery system. The key point is to use mixed anhydride groups as activating intermediates to mediate the synthesis of the ternary heparin conjugate. Formation of mixed anhydride is detected by the conductimetry experiment. The ternary heparin conjugate is characterized by (13)C NMR, FT-IR and GPC, respectively. The decreased trend on degree of substitution (DS) is consistent with that of introduced anticancer drug and specific ligand in drug delivery system. Moreover, their anticoagulant activity is evaluated by measuring activated partial thromboplastin time (APTT) and anti-factor Xa activity. The results show that model ternary heparin conjugate with reduced anticoagulant activity may avoid the risk of severe hemorrhagic complication during the administration and is potential to develop a safe and effective drug delivery system on anticancer research.
authors.affiliation: Biomedical Engineering Center, Hunan University, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dingcheng
authors.initials: D
authors.lastname: Xin
authors.forename: Jiawen
authors.initials: J
authors.lastname: Hu
authors.forename: Kaijian
authors.initials: K
authors.lastname: Liu
authors.forename: Jiangao
authors.initials: J
authors.lastname: Pan
authors.forename: Jiannan
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006493:Heparin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008968:Molecular Conformation; D010314:Partial Thromboplastin Time
chemical_list: D000812:Anhydrides; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006493:Heparin