The Preparation And Drug Delivery Properties Of Hydrogel Microspheres Based On Diels-alder Reaction

Hydrogel microspheres have caught more attention due to its special shape and size. The larger hydrogel hasn’t these characteristics. Hydrogel microspheres are widely used in biology, medicine, daily necessities, etc. The preparation methods and conditions of hydrogel microspheres have a great influence on its performance. The Diels-Alder reaction has some advantages such as mild reaction conditions, high yield and simplicity. In this thesis, the hydrogel microspheres were prepared by inverse emulsion crosslinking base on Diels-Alder reation. Then swelling properties and the drug release properies of hydrogel microspheres were observed separately. The main results are listed as follows:Firstly, using the diene-functionalized bipolymers poly(DMA-co-FM) and dienophile-functionalized polymers PEG-AMI as raw materials, liquid paraffin as oil phase, Span80 and OP-10 as emulsifiers, furfuryl methacrylate diene-functionalized bipolymers hydrogel microspheres were prepared by inverse emulsion crosslinking method. The hydrogel microspheres were characterized by FT-IR, SEM, TG and other instruments. The influence of reaction temperature, dosage of emulsifiers, oil/water volume ratio, stirring speed and other factors on particle appearance was studied. The best preparation conditions were determined as follows: The volume ratio of oil to water is 20:1, the dosage of emulsifier is 0.075 g/mL paraffin, mechanical stirring speed is 500 r/min, reaction temperature is 40 ℃, reaction time is 8 h. In these conditions, the as-prepared microspheres were close to spherical in shape. The average particle size of microspheres was about 5 μm. Then swelling properties and in vitro drug release behavior of hydrogel microspheres were also studied. The results show that furfuryl methacrylate diene-functionalized bipolymers hydrogel microspheres has a strong ability of swelling and a good control of delivery.Secondly, the diene-functionalized bipolymers poly(NIPA-co-INF) and dienophile-functionalized polymers PEG-PMI was synthesized and used as raw material, liquid paraffin as oil phase, Span80 and OP-10 as emulsifiers, itaconic anhydride diene-functionalized bipolymers hydrogel microspheres were prepared by inverse emulsion crosslinking method. The products were characterized by NMR, IR, TG, UV, SEM and other instruments. The low critical temperature, molecular weight distribution and water soluble properties of diene were studied. The water-solubility of dienophile was also studied. The influence of reaction conditions on particle appearance was studied. The best preparation conditions were determined as follows: The volume ratio of oil to water is 10:1, the dosage of emulsifier is 0.075 g/mL paraffin, magnetic stirring speed is 1000 r/min, reaction temperature is 25℃, reaction time is 20 h. Then swelling properties and in vitro drug release behavior of hydrogel microspheres were studied. The results show that the itaconic acid amide polymer hydrogel microspheres has a strong ability of swelling, and a good control of delivery.Thirdly, the diene-functionalized terpolymer poly(NIPA-co-DMA-co-INF) was also prepared by free radical copolymerization of NIPA, DMA and INF. The LCST of poly(NIPA-co-INF) was adjusted because DMA is water-soluble. Taking the diene-functionalized terpolymer poly(NIPA-co-DMA-co-INF) and dienophile-functionalized polymers PEG-PMI as raw materials, liquid paraffin as oil phase, Span80 and OP-10 as emulsifiers, terpolymer hydrogel microspheres were prepared by inverse emulsion crosslinking method. The low critical temperature, molecular weight distribution and water soluble properties of diene-functionalized terpolymer were studied. The influence of reaction conditions on the morphology of the hydrogel microspheres was discussed. The best preparation conditions were determined as follows: The volume ratio of oil to water is 10:1, the dosage of emulsifier is 0.1 g/mL paraffin, mechanical stirring speed is 500 r/min, reaction temperature is 35 ℃, reaction time is 12 h.Then swelling properties and in vitro drug release behavior of hydrogel microspheres were also studied. The results show that the terpolymer hydrogel microspheres have a strong ability of swelling.