Blood compatibility evaluations of poly(ethylene glycol)–poly(lactic acid) copolymers

Abstract

Poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) copolymers have been widely used for various biomedical applications. However, their hemocompatibility has not been clarified, which would lag their developments and clinical applications. In this work, we studied the effect of PEG–PLA copolymers on key human blood components in terms of their structure and bio-functions, including morphology and lysis of red blood cells, fibrinogen structure and conformation, and plasma and blood coagulation. To elucidate a structure–activity relationship, we used diblock PEG–PLA copolymers with different molecular weight, PEG(5 kDa)–PLA(25 kDa) and PEG(2 kDa)–PLA(2 kDa), abbreviated as PEG5k–PLA25k and PEG2k–PLA2k, respectively. The results show that the PEG–PLA copolymers at the concentration range studied in this work neither caused morphological alteration and lysis of red blood cells nor affected the oxygen delivery function and fibrinogen conformation. PEG5k–PLA25k from 10 to 100 mg/mL and PEG2k–PLA2k from 1.5 to 5 mg/mL disturbed the local microenvironments of fibrinogen molecules. PEG5k–PLA25k at up to 0.1 mg/mL did not interfere in the coagulation process of plasma or whole blood, while PEG2k–PLA2k from 0.1 mg/mL significantly interfered in the intrinsic plasma coagulation pathway and impaired whole blood coagulation. The results provide important information for the molecular design and clinical applications of PEG–PLA copolymers.