Preparation Of Alginate Composite Hydrogels And Their Controlled Release For Protein

Hydrogels have a crosslinked network that can absorb large amounts of water to swell without dissolving.Porosity is the key to determining hydrogel performance.Therefore,preparation of porous hydrogels with controlled 3D structure,uniform gel pore size and good pore connectivity has been mainly studied.Porous hydrogel,as a new material with rapid expansion and high water absorption,has great application value in traditional agriculture,tissue engineering,and biomedicine.Alginate is a linear block copolymer composed of poly?-L-guluronic acid?G?and poly?-D-mannuronic acid?M?.It is widely derived from natural raw material such as brown alginate and kelp.At the same time,alginate contains a large number of carboxylic acids and hydroxyl groups,and can be used to synthesize superabsorbent polymers with functional monomers.It is widely used in the field of drug carriers because of its excellent hydrophilicity.This paper aims to synthesize a series of pH-sensitive alginate/polymer composite hydrogels,and further study the swelling properties,pH sensitivity,and drug loading properties of the composite hydrogels,so as to lay a foundation for the development of environmentally friendly polymer materials with good drug slow-release properties.This thesis consists of four parts.In the chapter one,preparation and application of alginate polymer hydrogels are mainly introduced.Firstly,the classification,preparation methods and applications of hydrogels are reviewed.Secondly,the structure and modification of sodium alginate and the preparation of alginate composite hydrogel are introduced in detail.Finally,the application of alginate hydrogels in drug controlled release carriers,3D printing,tissue engineering scaffolds and enzyme fixation materials is reviewed.In the chapter two,alginate/polyacrylic acid composite hydrogels?APCGs?were prepared by solution polymerization in sodium alginate solution with acrylic acid?AA?as monomer,N,N'-methylene diacrylamide?BIS?as crosslinking agent and ammonium persulfate?APS?as initiator.The influence of acrylic acid dosage on the structure of hydrogel network was investigated.The structure of APCGs was characterized by FTIR,and SEM.The results show that the APCGs have a network structure with open and closed pores,and a pore diameter of about 0.8-1.0?m.The water absorption properties of APCGs were further studied.The maximum swelling degree of APCGs can reach to 180 g/g,and shows good pH sensitivity.Meanwhile,the loading performance of APCGs on bovine serum albumin?BSA?was investigated by using BSA as biomacromolecular drug.When the concentration of BSA was 4 mg/mL,the maximum drug loading of APCGs was 0.48 g/g.The BSA release was simulated in the environment of human administration.In the simulated intestinal pH 7.5,the cumulative release rate of BSA was 70%,showing a good drug sustained-release carrier capacity.While the cumulative release rate of BSA was less than 5%and almost no release in the simulated gastric pH 1.2.In the chapter three,alginate/polyacrylic acid hydrogels?G-APCGs?were prepared by adding porogen NaHCO_3.NaHCO₃ rapidly produces a large amount of CO₂ under an acidic background.In order to ensure that CO₂ gas is wrapped in the 3D network structure of G-APCGs during the polymerization process and achieve the purpose of pore formation.Meanwhile,TEMED is added to accelerate the formation of hydrogels.The G-APCGs have a network structure with open and closed pores by controlling AA and NaHCO₃ dosage.The pore diameter of G-APCGs is about 13-15?m,which is 15 times larger than APCGs.G-APCGs achieved shorter swelling equilibrium time and greater swelling degree in the water phase.The maximum water absorption of G-APCGs is 420 g/g,which is 200 times higher than APCGs.The maximum drug loading of G-APCGs was 0.34 g/g.The cumulative release rate of BSA can achieve 85%in simulated intestinal fluid?pH 7.5?,which is 15%higher than APCGs,while in the simulated gastric?pH 1.2?,the cumulative release rate of BSA was less than 7%.In the chapter four,alginate/polyacrylic acid hydrogels?T-APCGs?were prepared by template method with anionic surfactant sodium sodium dodecyl sulfate?SDS?,cationic surfactant cetyltrimethylamine bromide?CTAB?,non-ionic surfactant Tween 20 as the mold-forming agent.After the surfactant is dissolved in water,it self-assembles to form micelles.These micelles can be used as templates to form porous hydrogels.The effects of surfactant types and dosages on the network structure of T-APCGs were investigated.The pore diameter of T-APCGs is approximately 21-23?m by controlling the amount of SDS,which is 23 times larger than APCGs.The swelling degree of T-APCGs is higher than that of APCGs,and the highest swelling degree can reach 197 g/g.The maximum drug loading of T-APCGs is 0.19 g/g.Secondly,the cumulative release rate of BSA can reach 95%in simulated intestinal fluid?pH 7.5?,which is 25%higher than that of APCGs,while the cumulative release rate of BSA in simulated gastric fluid?pH 1.2?is lower than 10%,showing a good drug slow-release carrier ability.In this paper,a series of alginate polymer composite hydrogels?APCGs,G-APCGs and T-APCGs?were successfully prepared by using the natural polymer sodium alginate as raw material.The microstructure and pore size of the composite hydrogel were adjusted by controlling the dosage of monomer,pore-forming agent and surfactant.The hydrogel with higher water absorption was obtained.At the same time,the BSA release and load was simulated in the environment of human administration.It provides a theoretical basis for the next step in the preparation of new water-absorbent and water-retaining materials and intelligent drug sustained-release carriers.