Study on the Water Structure and Blood Compatibility of Poly(acryloylmorpholine-r-butyl methacrylate)

Abstract

We have been studying the blood compatibility of polymeric materials from the viewpoint of their water structure, and have proposed that freezable water interacting with polymer molecules plays an important role in determining that compatibility. As we found that water-soluble poly(acryloylmorpholine) interacted with water, resulting in the formation of 'bound water', we newly prepared water-non-soluble poly(acryloylmorpholine-r-butyl methacrylate) (denoted as ACMO co-polymer) with various composition ratios. In addition, the properties of a co-polymer based on N,N-diethylacrylamide (DEA co-polymer), where DEA has a similar chemical structure to ACMO, except that DEA has no ether oxygen, were compared with that of the ACMO co-polymer. Contact angle and DSC analysis revealed that an increase in the content of an N-substituted acrylamide unit in the co-polymers enhanced the hydrophilicity of the polymer and that the hydrophilicity of the ACMO co-polymer was stronger than that of the DEA co-polymer. As for the water structure, it was found that the ACMO co-polymer had a lot of bound water compared to the DEA co-polymer. The difference in these properties between the ACMO and DEA co-polymers was due to the ether oxygen of the morpholine group. At the same time, in vitro blood compatibility tests showed that the ACMO co-polymer exhibited a much better performance than the DEA co-polymer. The water structure and blood compatibility is discussed in detail.

Correlation between Protonation of Tailor-Made Polypiperazines and Endosomal Escape for Cytosolic Protein Delivery

“…All in all, the uptake of polymers seems to be rather low, particularly for P­(NAMP) 500 1C′ and P­(NAEP) 500 2C′ according to the flow cytometry data, which is surprising for cationic polymers. A reduced uptake could be explained with the polymers’ moderate degree of charge at pH 7.4 and their high structural similarities to P­(NAM), which is considered to suppress unspecific interactions similar to polyethylene oxide (PEO) or polyoxazolines. − …”

Recrystallization of Water in Non-Water-Soluble (Meth)Acrylate Polymers Is Not Rare and Is Not Devitrification

“…In other words, water molecules are maintained in the monomeric state at any T. This is mainly based on DSC analysis. No DSC signal from water sorbed into pBMA, 15 poly(n-butyl acrylate) (pBA), 20 and pMEA 20 as the analogue of pEEA and pEEMA has been reported. However, in the first place, there are not many reports on sorbed water by vapor sorption on the basis of DSC analysis.…”

“…The results of some studies on the relation of biocompatibility to water structure in aqueous polymer solutions − and non-water-soluble polymers − have been reported. Among them, the water structure in poly(2-methoxyethyl acrylate) (pMEA), which is a non-water-soluble polymer and a polymer with high blood compatibility, has been examined by differential scanning calorimetry (DSC), − X-ray diffraction spectroscopy, nuclear magnetic resonance spectroscopy, and mid-infrared (MIR) spectroscopy. − On the basis of results of DSC analysis, it was proposed that biocompatible polymers have “intermediate water” (cold-crystallizable water, recrystallized water, or freezing bound water). − “Intermediate water” was defined as water that is frozen (crystallized) only during heating. In the general definition in DSC, however, “intermediate water” is water that is frozen or molten at a lower temperature ( T ) than the thermodynamic melting T ( T m ) of water, 273 K, regardless of the direction of T change.…”

“…pTHFA is also a polymer with high blood compatibility. It was thought that recrystallized water in the two polymers also originated from glassy water and was in a condensed state, which had a special structure to avoid protein adsorption, at physiological T . − …”

Poly(tertiary amide acrylate) Copolymers Inspired by Poly(2-oxazoline)s: Their Blood Compatibility and Hydration States

“…Although coPAEA, coPPEA, and coPEAE did not perform ideally in antiplatelet adhesion, they reduced platelet adhesion compared with PBuA, especially in advanced activated platelets. Given that hydrophobic PBMA also showed low antiplatelet adhesion, 22,39 it can be ascertained that the PAEA, PAEM, PPEA, and PEAE segments improved blood compatibility. Micro BCA assay was conducted on copolymer cast 96-well TCPS plates to quantitively analyze the adsorbed plasma proteins, and ELISA was performed on copolymer spin-coated PET to investigate the exposure degree of the γ′ chains on adsorbed fibrinogen.…”