Study On Preparation And Properties Of Hydrogel Based On Alginate With PH And Temperature Sensitivity

In this thesis, naturally polymer sodium alginate (SA), which has biocompatibility and biodegradation, was chosen as one of the materials. The controllable degradation of oxidized sodium alginate (OSA) and its hydrogel were studied. The interactions between SA or OSA and bovine serum albumin (BSA) in aqueous solution were also investigated. Oxidized sodium alginate-graft-poly((2-dimethylamino)ethyl methacrylate) (OSA-g-PDMAEMA) gel beads, poly((2-dimethylamino)ethyl methacrylate)/oxidized sodium alginate semi-interpenetrating network (PDMAEMA/OSA Semi-IPN) hydrogel, poly((2-dimethylamino) ethyl methacrylate-co-glycidyl methacrylate)/alginate (P(DMAEMA-co-GMA)/SA) Semi-IPN hydrogel and modified sodium alginate/poly(acrylic acid) (MSA/PAA) nanogel were prepared. The hydrogels were characterized by Fourier transform infrared (FTIR) spectroscopy,H NMR spectrum, scanning electron microscopy (SEM), transmission electron micrograph (TEM) and differential scanning calorimetry (DSC), and their pH, temperature and ionic strength sensitivity were investigated. Meanwhile, the drug release behaviors of these hydrogels were explored on different conditions. The main results were shown as follows:1. OSA with different degree of oxidation was prepared using sodium periodate (NaIO4), and the degradation of OSA in PBS was studied. Calcium carbonate (CaCO3) in combination with D-glucono-δ-lactone (GDL) was used as a source of calcium ions to initiate the gelation of OSA. The interior morphology of OSA hydrogels was examined by SEM, the degradation of OSA hydrogels was investigated in PBS and Tris-HCl and the mechanism of degradation was evaluated by DSC. The results showed that the OSA with different degree of oxidation can be obtained by varying the ratio of NaIO4 to the number of repetitive units of SA. With the increased in the amount of NaIO4, the degree of oxidation increased and the molecular weight decreased. The degradation behavior of OSA and its hydrogel relied heavily on the degree of oxidation. The higher the degree of oxidation is, the faster the degradation rate is. The work provided a theory basis for the controllable degradation of SA based hydrogels. 2. The interactions between OSA and BSA were investigated by fluorescence spectroscopy and UV/vis absorption spectroscopy. The cytotoxicity of OSA with different degree of oxidation was quantitatively assessed by MTT assay. The results showed that OSA can strongly quench the intrinsic fluorescence of BSA through a static quenching. OSA-BSA complex was formed by hydrogen bonds and electrostatic interactions, and the binding of OSA with BSA cannot induce conformational changes in BSA. The OSA with a lower degree of oxidation (< 30%) is almost non-toxic, and has a potential as a drug carrier.3. Amino group-terminated PDMAEMA-NH2 was grafted onto OSA by C=N bond, and the gel beads of OSA-g-PDMAEMA were prepared in an aqueous solution of CaCl2. The effects of pH and ionic strength on the swelling behaviors of the gel beads were studied. BSA was chosen as a model drug and the in vitro drug release profiles were studied. The results showed that OSA-g-PDMAEMA gel beads have pH and ionic strength sensitivity. The drug release can be controlled by adjusting the graft percentage and the pH of the solution, the PDMAEMA chains could reduce the drug release rate in pH 7.4.4. PDMAEMA/OSA Semi-IPN hydrogel was prepared by a reaction of DMAEMA and OSA with ammonium persulfate (APS) as an initiator, N, N'-methylenebisacrylamide (NNMBA) as a crosslinker and PDMAEMA microgel as an additive. The hydrogels were characterized by FTIR, SEM and DSC. The swelling/shrinking, pH and temperature sensitivity of the hydrogels were studied. The effect of pH on the drug release was also investigated. The results showed that the pore size in the hydrogel network can be adjusted by changing the amount of PDMAEMA microgels. The higher the amount of PDMAEMA microgels is, the quicker the swelling/shrinking is. The drug release rate was depended on the pore size and pH of the solution.5. P(DMAEMA-co-GMA)/SA Semi-IPN hydrogel was synthesized via radical polymerization of the double bonds and ring-opening of the epoxy groups.'H NMR and FTIR were consistent with the expected structures for the hydrogels. The interior morphology of the hydrogels was also investigated by SEM. The release behavior of the model drug was studied. The cytotoxicity and biocompatibility of the hydrogels were assessed by MTT assay and the protein adsorption and denaturation experiment. The results showed that P(DMAEMA-co-GMA)/SA Semi-IPN hydrogels have pH and temperature sensitivity. The mechanical strength of semi-LPN hydrogels was enhanced by the introduction of alginate chains. The release behavior of the drug was found to be dependent on the hydrogel composition and environment pH. P(DMAEMA-co-GMA)/SA Semi-IPN hydrogels also have no toxicity, the hydrogels can not semi-IPN hydrogels could not make the protein denaturation.6. MSA/PAA nanogel was prepared by glycidyl methacrylate modified sodium alginate and acrylic acid using emulsion polymerization. The nanogels were characterized by FTIR, TEM and elemental analysis. The effect of pH and ionic strength on the nanogels solution were studied, and the drug release was also studied. The cytotoxicity of MSA/PAA nanogels was quantitatively assessed by MTT assay. The results showed that the size of the nanogels was 50-100 nm. The nanogels have a faster response rate to pH and ionic strength, the smaller the size is, the faster the phase transition. The drug release behaviors depended on the linear size and the medium pH. The nanogels have no toxicity and can be used as drug carrier to the colon.