Study On Temperature/pH Dual Responsive Alginate Aerogel And Its Application In Drug Delivery

Aerogel with low density,high specific surface area,high porosity and other excellent properties,has a wide range of applications in catalysts,adsorbents,thermal or noise insulation materials,drug carriers and other materials.With the development of biocompatible inorganic aerogels and biodegradable polysaccharide-based organic aerogels,surface-functionalized aerogels and composite aerogels with great potential are also under development.Because of high porosity,aerogel has attracted progressively increasing attention as drug carrier.A novel alginate-g-poly(N-isopropylacryamide-co-N-hydroxymethyl-acrylamide)copolymer with environmental responsiveness was successfully prepared by grafting N-isopropylacryamide and N-hydroxymethyl-acrylamide into sodium alginate.and a novel dual-response polysaccharide-based aerogel with thermo/pH sensitivity was designed used the copolymer as a drug controlled release system.Studies were shown that lower critical phase transition temperature(LCST)of alginate-g-poly(N-isopropylacryamide-co-N-hydroxymethyl-acrylamide)graft copolymer can be adjusted by changing the ratio between N-isopropylacryamide and N-hydroxymethyl-acrylamide.Moreover the occurrence of grafting reaction enhanced the thermal stability of alginate.Alginate-g-poly(N-isopropylacryamide-co-N-hydroxymethyl-acrylamide)aerogel was prepared by GDL-Ca2+ cross-linking.And it possessed a three-dimensional network structure with low density(0.395g/cm3)and high porosity(97.9%)which can load more drugs.The maximum loading of the hydrophobic drug(indomethacin)was 13.24%;for the hydrophilic drug(sodium salicylate),the maximum loading was reached 82.01%.The prepared aerogel was responsive to both temperature and pH.Above LCST,the drugs from aerogels were released more quickly and the amount of drugs was released more.The aerogel had a faster drug release,and drug was completely released in neutral environment,while the drug release was obstructed in acid environment.Hydrophobic drug-loaded drug carriers are more responsive than hydrophilic drug carriers.It can be concluded that for hydrophobic drugs,above LCST,the release mechanism is dominated by Fickian diffusion.However,below LCST,the release mechanism,in addition to diffusion,is accompanied by the occurrence of skeleton dissolution.For hydrophilic drugs,the mechanism of release is diffusion above and below the LCST,and burst release occurred at the initial stage of drug release.The research results of this thesis provide a new possibility for the application of functional aerogel in the field of drug carrier.