Study on the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rat of OX26 conjugated endomorphin loaded HBPG-PLGA nanoparticles

Abstract

Objective To study the cytotoxicity against brain microvessel endothelial cells and blood compatibility in rats of OX26 conjugated endomorphin (EM) loaded hyperbranched polyglycerols-poly(lactic-co-glycolic acid)(HBPG-PLGA) nanoparticles.Methods Prepared nanoparticles were divided into group B (HBPG-PLGA nanoparticles),group EP (EM-HBPG-PLGA nanoparticles) and group OEP (OX26-EM-HBPG-PLGA nanoparticles).The cytotoxicity against brain microvessel endothelial cells (BMECs) of nanoparticles of different groups were measured by MTT test,haemolysis test,normal haemotological parameter and several primary items of coagulation system were tested after nanoparticles of different groups and different dosages injection on rats.Results ①All the three groups of nanoparticles induced decreased cell viability in a dose dependent manner in MTT test,whereas all groups of nanoparticles showed low cytotoxicity against the BMECs during 30 to 600 μg/ml.②There was no significant difference in haemolysis ratio (P＞0.05) and normal haemotological parameter (P＞0.05).③There was no significant difference between the low dosage of all the three groups of nanoparticles and the control group on the function of coagulation system in rats (P＞0.05).④Compared with C group,high dose groups demonstrated longer prothrombin time (PT),activeated partial thromboplasting time (APTT) and lower fibrinogen (Fbg) (P＜0.05).At the same time,compared with the low dose subgroups,PT and APTT were prolonged,Fbg significantly decreased in the high dose subgroups (P＜0.05 or P＜0.01).Conclusion OX26 coupled with EM-HBPG-PLGA nanoparticles showed low cytotoxicity against BMECs and had no significant effect on the coagulation system in rats with low concentration and low dosage. Key words: Nanoparticle; Cytotoxicity; Haemolysis; Normal haemotological parameter; Coagulation system; Bio-safety