In-Situ Injectable Physically and Chemically Gelling NIPAAm-Based Copolymer System for Embolization

Abstract

The goal of this work is to make an injectable physically and chemically cross-linking NIPAAmbased copolymer system for endovascular embolization. A copolymer with N-isopropylacrylamide (NIPAAm) and hydroxyethyl methacrylate (HEMA) was synthesized and converted to poly (NIPAAm-co-HEMA-acrylate) functionalized with olefins. When poly(NIPAAm-co-HEMAacrylate) was mixed with pentaerythritol tetrakis 3-mercaptopropionate (QT) stoichiometrically in 0.1 N PBS solution of pH 7.4, it formed a temperature-sensitive hydrogel with low swelling through the Michael-Type Addition reaction and showed improved elastic properties at low frequency compared to physical gelation. This material could be useful for applications requiring water-soluble injection but lower swelling and lower creep properties than available with other soluble in situgelling materials.

Poly(N‐isopropylacrylamide‐co‐poly(ethylene glycol))‐acrylate simultaneously physically and chemically gelling polymer systems

“…[2][3][4] Moreover, because these temperature-responsive systems are water-soluble, they can potentially act as alternatives to in vivo-gelling materials/embolic liquids [3][4][5][6] that are traditionally delivered via watermiscible, but toxic, organic solvents such as dimethyl sulfoxide (DMSO), ethanol, and N-methyl pyrrolidone (NMP). 4,7 While these thermo-sensitive polymers exhibit many desirable characteristics, they are constrained by their tendency to creep under low frequency stress, which renders them unsuitable for applications that require long-term functional replacement such as arteriovenous malformation (AVM) or aneurysm occlusion. 4 Thus, there is a need to develop polymer systems that have the ability to address the mechanical limitations of these temperature-responsive materials.…”

Injectable hydrogels

“…46 Usually, solutions are formulated at <30 wt % and deswell such that the final polymer concentration in the gel is about 50%, [47][48][49][50] so a significant fraction of water is lost during gelation. Rapid deswelling and syneresis (i.e., loss of the initially entrapped aqueous liquid) has been shown to be associated with fast drug release on heating above the LCST of NIPAAm-based physical gels.…”

“…277,278 Physical-Chemical Gels Gels that cross-link both physically and chemically have potential to combine the advantages of fast gelation typical of temperature-responsive physical gels with the strength and elasticity of a covalently cross-linked material. Combining poly(NIPAAm-co-HEMA-acrylate) with either thiol-functionalized poly(NIPAAm) 279,280 or thiol-functionalized crosslinkers 50 yields stronger gels with improved elastic properties at low frequency compared with physical gels. Alternatively, thiol-functionalized poly(NIPAAm) forms strong and elastic physical-chemical gels on mixing with PEGDA below the LCST, which, when heated, reach storage moduli near 1 MPa, an exceptionally high value for a hydrogel.…”

Microfluidic chip containing porous gradient for chemotaxis study

“…Gtn-HPA conjugates were prepared as described by Lee et al [6] using a general carbodiimide/active ester-mediated coupling reaction in distilled water. The CMC-Tyr conjugates were prepared by adding carboxymethyl cellulose CMC and tyramine hydrochloride (Tyr) to milliQ water.…”