PEGylation of Lumbrokinase improves pharmacokinetic profile and enhances anti‑thrombotic effect in a rat carotid artery thrombosis model.

The present study aimed to prepare injectable Lumbrokinase (LK) with long circulation time in addition to enhanced anti-thrombotic efficacy. Following preparation, the pharmacokinetic and anti‑thrombotic effect of the drug in a rat carotid artery thrombosis model was evaluated. The drug was prepared by conjugation of LK with mPEG‑SC20000 as previously reported. The pharmacokinetics of the mPEG‑SC20000‑LK were then examined and the anti‑thrombotic activity in an artery‑vein bypass thrombosis rat model was evaluated. Finally, the parameters of fibrinolysis including thromboxane B2, prostaglandin F1α, tissue plasminogen activator and plasminogen activator inhibitor‑1 were compared between native LK and mPEG‑SC20000‑LK in a FeCl3‑induced carotid artery thrombosis rat model. mPEG‑SC20000‑LK was successfully prepared by PEGylation of LK with mPEG20000‑SC in optimal conditions. Pharmacokinetic analysis demonstrated that the biological half‑life of the mPEG20000‑SC‑LK increased by 2.2‑fold compared with native LK. In vivo anti‑thrombotic analysis indicated that mPEG20000‑SC‑LK exhibited a greater anti‑thrombotic effect in artery‑vein bypass thrombosis and FeCl3-induced carotid artery thrombosis models compared with native LK. In conclusion, injectable PEGylated LK with prolonged half-life and enhanced anti‑thrombotic effect is a potential anti‑thrombotic agent for long‑acting treatment of the thrombus diseases.