Application of thermosensitive polymers as a new embolic material for intravascular neurosurgery

Abstract

Application of thermosensitive polymers as an embolic material for intravascular neurosurgery was investigated. We intended to use thermosensitive polymers to occlude vessels by precipitation in response to body temperature. Copolymers of N-isopropylacrylamide (NIPAM) and N-n-propylacrylamide (NPAM) were selected as thermosensitive polymers. To determine the optimal lower critical soluble temperature (LCST) for the embolic material, we developed an in vitro flow model. In this study the copolymers with an LCST of 24-26 degrees C showed appropriate precipitation. To prove the occlusion of vessels in vivo, we injected the copolymers into a rabbit kidney through a microcatheter. The extent of embolization was judged by angiography and histological examination. An acute toxicity test of the copolymer of NIPAM and NPAM was performed in comparison with that of the NIPAM monomer. The copolymer used in this paper showed no acute toxicity in mice. Water solubility, non-adhesiveness, and non-toxicity are the advantages of the use of thermosensitive polymers as an embolic material. By changing the LCST, various embolic materials can be designed. Based on our results, we believe that the application of thermosensitive polymers as a new embolic material is very promising.

N‐Isopropylacrylamide/2‐Hydroxyethyl Methacrylate Star Diblock Copolymers: Synthesis and Thermoresponsive Behavior

“…[24] The bands at 1 650 and 1 538 cm À1 are assigned to amide I and amide II, respectively. 1 H NMR spectra of PHEMA and copolymers (DMSO-d 6 , not shown) demonstrated the feature signals of HEMA (OH: [19] and NIPAAm bands (NH: d ¼ 7.2; -CH 2 -CH-: d ¼ 1.5; -CH 2 -CH-: d ¼ 1.9; -CH(CH 3 ) 2 : d ¼ 1.9; -CH(CH 3 ) 2 : d ¼ 3.9). [25] Although the characteristic peaks of two units are overlapped to a certain degree, the signals of PNIPAAm block are enhanced with the increase of NIPAAm content in copolymers, implying the formation of longer star-like diblock copolymers at higher NIPAAm ratios.…”

“…[5,6] These systems are in the sol state at low temperatures, and gel at elevated temperatures. Among these thermoresponsive polymers reported to date, poly(N-isopropylacrylamide) (PNIPAAm) is of particular interest due to its sharp transition and established response mechanism.…”

An l-proline based thermoresponsive and pH-switchable nanogel as a drug delivery vehicle

“…33 Acryloyl chloride (1.53 g, 17 mmol) was dissolved in toluene (50 mL) and stirred under a N 2 atmosphere at −78°C (using an acetone-dry ice bath). N-Propylamine (2 g, 34 mmol) was added dropwise to the solution for 30 min.…”

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

“…[1][2][3] Their characteristic temperature-driven sol-gel transition is advantageous in terms of implantation because it allows the material, in fluid form, to fully conform to its surroundings before gelling in vivo. [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.…”