Microfluidic synthesis of thermo-responsive poly(N-isopropylacrylamide)–poly(ethylene glycol) diacrylate microhydrogels as chemo-embolic microspheres

Abstract

In this paper, we have successfully synthesized and characterized poly(N-isopropylacrylamide) (PNIPAAm)–poly(ethylene glycol) diacrylate (PEGDA) microhydrogels. Various combinations of PNIPAAm-PEGDA microhydrogels were fabricated by the generation of monodisperse microdroplets whose sizes were comparable to a blood vessel of 260 and 320 µm with the help of a hydrodynamic focusing microfluidic device (HFMD), followed by synthesis of the microhydrogels through UV irradiation to the microdroplets. The thermo-responsive behaviors of the various microhydrogels were investigated by changing the PEGDA crosslinker concentration, which was found to be a dominant factor in tuning the shrinkage ratio in response to temperature change. As an in vitro embolization performance evaluation of the microhydrogels as chemo-embolic microspheres, the deliverability of the microhydrogels through a microcatheter was first confirmed and the compact occlusion of a channel was demonstrated based on a tapered microchannel in response to the temperature increase to physiological temperature of 36 °C. The controlled release behavior of the fluorescent dye from the microhydrogel was also investigated for chemotherapeutic purposes as a proof of concept study. The PNIPAAm-PEGDA microhydrogels could be used widely in embolization procedures based on the advantages of tunable thermo-responsive and controlled release behaviors.

Stabilizing Coacervate by Microfluidic Engulfment Induced by Controlled Interfacial Energy

“…First, coacervate and PEGDA solutions were separately injected as two distinct streams into a hydrodynamic focusing microfluidic device (HFMD) (Figure S4) using a syringe pump. Subsequently, the injected two disperse phases were merged and broken into microdroplets by the continuous oil phase at the orifice of HFMD due to capillary instability. − The Janus-shaped microdroplets composed of coacervate and PEGDA were observed near the orifice of HFMD (Figure C). The shape of microdroplets was changed from Janus to core–shell morphology along the direction of downstream flow in the microchannel, shown in the inset of Figure C.…”

“…Two cured PDMS replicas were bonded together after oxygen plasma treatment. The detail design parameters and fabrication procedure are shown in Figure S4. − …”

High-Performance Poly(lactic-co-glycolic acid)-Magnetic Microspheres Prepared by Rotating Membrane Emulsification for Transcatheter Arterial Embolization and Magnetic Ablation in VX2 Liver Tumors

“…However, the majority so far are permanent, polydispersed, and irregularly shaped . Therefore, the embolic agents mentioned above would suffer high risks regarding post-embolization syndromes and are unable to precisely control the level of embolization. , Thus, the biodegradable, regularly shaped and uniform sized microspheres should be preferred . Kirchhoff and co-workers used the degradable starch microspheres (Spherex, Pharmacia, Erlangen, Germany) for the TACE procedure .…”

Synthesis of Poly(<em>N</em>-isopropylacrylamide) Janus Microhydrogels for Anisotropic Thermo-responsiveness and Organophilic/Hydrophilic Loading Capability

“…25,26 The microfluidic approach is at the forefront of research as a means of fabricating micro-sized particles with narrow size distributions and complex shapes. [27][28][29][30][31] The advantages of fabricating microparticles in the microfluidic device are predicated by the small characteristic length of the microfluidic device, which results in a low Reynolds number. In contrast to traditional bulk emulsification where drops are formed in parallel, microdroplets produced in microfluidic devices are generated in series and subsequently polymerized into microparticles upon exposure to UV irradiation.…”