Tunable Blood Compatibility of Polysulfobetaine from Controllable Molecular-Weight Dependence of Zwitterionic Nonfouling Nature in Aqueous Solution

Abstract

This work describes a tunable blood compatibility of zwitterionic poly(sulfobetaine methacrylate) (polySBMA) polymers at a wide range of high molecular weights from 50 kDa to 300 kDa controlled with a similar polydispersity via homogeneous free-radical polymerization. The control of molecular weights of polySBMA highly regulates the zwitterionic nonfouling nature to resist the adsorption of plasma proteins, the coagulant of human plasma, and the hemolysis of red blood cells. In this study, the upper critical solution temperatures (UCSTs) and hydrodynamic size of prepared polymers are determined to illustrate the correlations between intermolecular zwitterionic associations and blood compatibility of polySBMA suspension in human blood. The polySBMA exhibited clear shifts of UCSTs in the stimuli-responsive control of solution pH and ionic strength, which were strongly associated with the molecular weights of the prepared polymers. Plasma-protein adsorption onto the polySBMA polymers from single-protein solutions and the complex medium of 100% human plasma were measured by dynamic light scattering to determine the nonfouling stability of polySBMA suspension. It was found that the nonfouling nature as well as hydration capability of polySBMA can be effectively controlled via regulated molecular weights of zwitterionic polymers. This work shows that the polySBMA polymer with an optimized molecular weight of about 135 kDa at physiologic temperature is presented high hydration capability to function the best nonfouling character of anticoagulant activity and antihemolytic activity in human blood. The excellent blood compatibility of zwitterionic polySBMA along with their stimuli-responsive phase behavior in aqueous solution suggests their potential for use in blood-contacting targeted delivery and diagnostic applications.