title: Immunotargeting of collagenase on thrombus.
abstract: In this study, we aimed to develop a thrombus-targeting delivery system of collagenase bound to a monoclonal antibody, and to investigate the thrombolysis of an immune-conjugate in vitro and in vivo as well as the targeting effect. We prepared the immunizing conjugation of collagenase by the 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDCI) method. In order to conjugate collagenase and a monoclonal antibody, bovine serum albumin was used as a linker, increasing the number of collagenase molecules carried and keeping collagenase and the monoclonal antibody active. In vitro thrombolysis experiments showed that collagenase had a strong dissolving effect on collagen-embolus within 24 hours. We established a rabbit pulmonary embolism model to investigate the thrombolysis effect of collagenase and collagenase immunizing conjugation in vivo. Our results revealed a significant difference between collagenase and collagenase immunizing conjugation (P < 0.05). We also established a rabbit ear edge vein model to investigate the active target of collagenase immunizing conjugation. We found that collagenase immunizing conjugation had active targets, and had a strong ability to dissolve organized thrombi. In conclusion, the thrombus-targeting delivery system of collagenase we developed has active targeting effects on thrombi.
authors.affiliation: Key Laboratory of Drug Targeting and Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yi-ling
authors.initials: YL
authors.lastname: Lu
authors.forename: Ben-xia
authors.initials: BX
authors.lastname: Yang
authors.forename: Zong-ning
authors.initials: ZN
authors.lastname: Yin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D002417:Cattle; D017364:Collagenases / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004423:Ear / Q000098:blood supply; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry; D006651:Histocytochemistry; D000922:Immunotoxins / Q000008:administration & dosage* / Q000737:chemistry; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D011651:Pulmonary Artery; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011817:Rabbits; D012044:Regression Analysis; D012710:Serum Albumin, Bovine / Q000737:chemistry; D015912:Thrombolytic Therapy / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D000922:Immunotoxins; D012710:Serum Albumin, Bovine; D017364:Collagenases