Preparation Of Poly(N-isopropylacryamide-co-methacrylic Acid) Hydrogel Microspheres By Microfluidic Method

Poly(N-isopropylacrylamide)(PNIPA)microgel is one of the typical thermos-responsive hydrogels that swell at low temperature and shrink at high temperature.The volume phase transition temperature(VPTT)of PNIPA microgel is about 33 ℃ and it can be improved by copolymerizing with hydrophilic monomer such as methacrylic acid(MAA).This kind of microgel is widely used as drug carriers because its VPTT is closed to the physiological temperature.For PNIPA microgels prepared by conventional emulsion polymerization,there are some defects such as the removal of the emulsifier,uncontrolled size and uncertain drug loading rate.Microfluidics technology developed in recent years can be used to solve these problems.In order to optimize the synthesis condition of hydrogel microspheres prepared by microfluidic method,the poly(N-isopropylacrylamide-co-methacrylic acid)(P(NIPA-co-MAA))hydrogel was first prepared by photoinitiated free radical polymerization in ethanol/water.The effect of the monomer ratio on the hydrogel response behavior was investigated.Then P(NIPA-co-MAA)hydrogel microspheres with solid structure and core-shell structure were prepared based on self-made microfluidic device.The effects of surfactants and the flow rates of continuous phase and dispersed phase on the size of hydrogel microspheres were discussed.The temperature and p H response of the hydrogel microspheres were studied by polarized light microscopy with a hot stage and optical microscopy.The release process of internal oil droplets of P(NIPA-co-MAA)core-shell hydrogel microspheres was observed.The main research results are as follows:1.P(NIPA-co-MAA)hydrogel was prepared by photo-initiated free radical polymerization in ethanol/water mixed solvent.The effects of solvent ratio and monomer composition on the hydrogel morphology and response behavior were discussed.The results show that the photopolymerization can be completed in 30 min.SEM results show that the hydrogels prepared in ethanol/water mixed solvent tend to form dense internal structure with many micropores,which can enhance the mechanical properties of hydrogels.The monomer ratio has a significant influence on the response behavior of P(NIPA-co-MAA)hydrogel.The VPTT of the hydrogel enhanced gradually with the increase of MAA content,moreover,the p H-responsive performance,swelling and deswelling rates increased obviously.2.P(NIPA-co-MAA)solid hydrogel microspheres with uniform structure and good monodispersity were prepared by self-made microfluidic chip.The results show that the size of the microspheres can be effectively controlled by adjusting the flow rates of the continuous phase and the dispersed phase and the content of the surfactant in the continuous phase.The temperature and p H response properties of the hydrogel microspheres were tested by polarized light microscopy with a hot stage and optical microscopy.The results show that the hydrogel microspheres swell at low temperature and shrink at high temperature.With the increase of MAA content,the VPTT of microspheres increased gradually and the p H response can be observed more obviously.3.The uniform-sized core-shell P(NIPA-co-MAA)hydrogel microspheres were prepared by double-coaxial microfluidic chip.The core of the microspheres was soybean oil which contained an oil-soluble fluorescent dye as the model of hydrophobic drugs and the shell was consisted by P(NIPA-co-MAA)hydrogel.The release process of oil core in the microspheres was studied.It was found that when the temperature was below the VPTT of P(NIPA-co-MAA),the microspheres were always in swollen state,but when the temperature was higher than its VPTT,the shell hydrogel shrank due to the temperature sensitivity,which provided the extrusion force on the inner core.As the increase of temperature,the inner oil core gradually deformed and then released from the hydrogel microspheres.