Low‐Fouling Zwitterionic Polymeric Colloids as Resuscitation Fluids for Hemorrhagic Shock

Abstract

Colloids, known as volume expanders, have been used as resuscitation fluids for hypovolemic shock for decades, as they increase plasma oncotic pressure and expand intravascular volume. However, recent studies show that commonly used synthetic colloids have adverse interactions with human biological systems. In this work, a low‐fouling amine(N)‐oxide‐based zwitterionic polymer as an alternative volume expander with improved biocompatibility and efficacy is designed. It is demonstrated that the polymer possesses antifouling ability, resisting cell interaction and deposition in major organs, and is rapidly cleared via renal filtration and hepatic circulation, reducing the risk of long‐term side effects. Furthermore, in vitro and in vivo studies show an absence of adverse effects on hemostasis or any acute safety risks. Finally, it is shown that, in a head‐to‐head comparison with existing colloids and plasma, the zwitterionic polymer serves as a more potent oncotic agent for restoring intravascular volume in a hemorrhagic shock model. The design of N‐oxide‐based zwitterionic polymers may lead to the development of alternative fluid therapies to treat hypovolemic shock and to improve fluid management in general.

Medicinal Chemistry of Drugs with N-Oxide Functionalities

“… 9 Furthermore, oligomeric N -oxides have the potential to serve as substitutes for other hydrophilic oligomers and polymers, such as polyethylene glycol (PEG). Recent studies revealed that these oligomeric N -oxides have excellent blood compatibility 10 and can be used as stealth reagents for the conjugation to drugs or material surfaces. 11 As many of the underlying principles have only recently been discovered, 12 the number of applications of N -oxides in the healthcare field is currently rapidly growing.…”

Reusable Zwitterionic Porous Organic Polymers for Bilirubin Removal in Serum

“…Zwitterionic materials, bearing opposite charges equally distributed at a molecular level, are highly biocompatible due to the superior anti-biofouling properties derived from the strong hydration effect via ionic solvation . They have been widely used as excellent biomaterials in various blood-contacting devices in recent years. ,,,− In this work, we installed three types of zwitterionic units, including carboxybetaine methacrylate (CB), sulfobetaine methacrylate (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC), into the POPs using a one-pot solvothermal free radical polymerization, which is a simple but promising strategy to develop functionalized POPs with remarkable adsorption properties. ,,, The low-cost commercially available divinylbenzene (DVB) was employed to form the rigid porous frameworks that may provide favorable interactions with the aromatic structure of bilirubin. The formed zwitterionic POPs exhibited excellent hemocompatibility and protein-resistant ability and efficient adsorption toward bilirubin in 100% fetal bovine serum (FBS) (Figure ).…”