Synthesis and evaluation of cationic polymeric micelles as carriers of lumbrokinase for targeted thrombolysis

Publication date: Available online 10 May 2018Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Yang Pan, Xiahui Wang, Zongning YinAbstractTo achieve targeted thrombolysis, a targeted delivery system of lumbrokinase  (LK) was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GPⅡb/Ⅲa expressed on the surface of membrane of activated platelet, LK loaded targeted micelles (LKTM) can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly (2-(dimethylamino) ethyl methacrylate) (PCL-PDMAEMA), methoxy polyethylene glycol-block- polycaprolactone (mPEG-PCL) and RGDfk conjugated polycaprolactone-block- polyethylene glycol (PCL-PEG-RGDfk). PCL-PDMAEMA was synthesized via ring open polymerization (ROP) and atom transfer radical polymerization (ATRP). PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bl...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research