| The supramolecular hydrogels based on the host-guest interactions betweenα-cyclodextrin and polymeric guest molecules have potential applications as drug carriers, biosensors, scaffolds for tissue engineering and other biomaterials due to their mild preparation conditions, easy modulation for the gelation process and injectable properties. Up to now, the studies on these hydrogels are limited to the methods of preparation, characterization of physical properties and applications in drug delivery, there are few reports on their functionalization modification. In view of this, this dissertation focuses on the preparation of functional supramolecular hydrogels by modifying polymeric guest molecules or incorporating functional inorganic nanoparticles. The gelation kinetics and microstructures of the hydrogels were characterized by the rheometer, scanning electron microscopy (SEM), X-ray diffractometer and so on. In addition, the applications of these hydrogels as durg carriers, gene carrier, antibacterial material and biosensor were also explored.1. Supramolecular hydrogels based on functionalized polymeric guests(1) A supramolecular hydrogel for hydrophobic drug (indomethacin) delivery was prepared by the host-guest interactions between indomethacin-modified polyethylene glycol (MPEG-indo) andα-cyclodextrin (α-CD). The X-ray diffraction (XRD) characterization confirmed thatα-CD threaded onto the MPEG segments of MPEG-indo to form a channel-type supramolecular structure. The rheological measurements were used to study the effects ofα-CD or MPEG-indo concentration on the gelation kinetics and rheological properties of the resultant hydrogels. It was found that with the increase ofα-CD or MPEG-indo concentration, the gelation time decreased and the hydrogel strength increased. The supramolecular hydrogels have shear-thinning and thixotropic properties, and their viscosity and thixotropy increased with the increase ofα-CD or MPEG-indo concentration. The in vitro release experiments showed a controlled and sustained release of MPEG-indo from the hydrogels, and the release rate increased with the decrease ofα-CD or MPEG-indo concentration. Moreover, the MPEG-indo was released in the form ofα-CD/MPEG-indo inclusion complexes, and their release behavior could be described by the Higuchi diffusion equation. The released MPEG-indo hydrolyzed by plasma showed an obvious inhibition effect to Hep-2 cells, and the inhibition ratio was over 40%.(2) In an attempt to develop a new supramolecular hydrogel with biological activity, heparin was used to conjugate with amino-terminated poly(ethylene glycol) methyl ether (MPEG), and then the modified MPEG (Hep-MPEG) was used to interact withα-CD in aqueous solution. The resultant hydrogel was characterized by XRD to confirm its supramolecular structure. The rheological measurements were used to study the effects ofα-CD or Hep-MPEG concentration on the hydrogel formation. It was found that with the increase of Hep-MPEG orα-CD concentration, the gelation time decreased and the hydrogel strength increased. The hydrogels have the shear-shinning property and thixotropic nature, which could flow under a high shear force and recover rapidly to a gel state after the force vanished. After encapsulating the bovine serum albumin (BSA) into the hydrogel, the supramolecular hydrogel was studied as a dual-drug carrier for the release of BSA and Hep-MPEG. It was found that the higher concentration of Hep-MPEG orα-CD induced the decrease of release rate. And the release mechanisms of two drugs were different, the BSA showed the non-Fickian diffusion behavior and the Hep-MPEG was fit to the Fickian diffusion model. By the blood clotting and haemolysis experiments, such a supramolecular hydrogel was confirmed to show good bioactivities with good anticoagulant and blood-compatible properties (hemolysis ratio≤5%).(3) Based on the host-guest interactions betweenα-CD and Pluronic F-68 modified by poly(L-lysine) (F-68-PLL), a new supramolecular hydrogel used as gene carrier was prepared. The copolymer F-68-PLL firstly formed stable complex micelles with DNA in aqueous solution, and then the DNA was encapsulated into the hydrogel in situ by the host-guest interactions. The XRD characterization confirmed the formation of such a supramolecular-structured hydrogel. The rheological characterization showed the effects ofα-CD or F-68-PLL concentration and DNA content on the hydrogel properties. It was found that with the increase ofα-CD or F-68-PLL concentration, the gelation time decreased and the hydrogel strength increased. The increased DNA content also made the gelation process faster and enhanced the hydrogel strength. Agarose gel electrophoresis was performed and confirmed that the hydrogels could inhibit the migration of DNA in the electric field. From the in vitro release experiments, it was found that the supramolecular hydrogel showed a controlled and sustained release of DNA. The increase ofα-CD or F-68-PLL concentration induced the decrease of the release rate. Furthermore, the DNA was released in the form of its complexes electrostatic-bonded with F-68-PLL. The DNA/F-68-PLL complexes were colloidally stable, preserved the integrity of supercoiled plasmid DNA, and gave good transfection efficiency (15%) in vitro. The MTT analysis showed that the hydrogel have a good biocompatibility.2. Supramolecular hydrogels incorporated with functional inorganic nanoparticles(1) A new strategy was developed for the fabrication of magnetically supramolecular hydrogels, in which colloidal stable magnetic iron oxide nanoparticles was firstly prepared by an amphiphilic poly(ε-caprolactone)-poly(ethylene glycol)- poly(ε-caprolactone) (PCL- PEG-PCL) block copolymers and then mixed with an aqueous solution ofα-cyclodextrin (α-CD). The PCL- PEG-PCL functioned as not only the dispersant for magnetic nanoparticles, but also the guest molecules for the formation of the hydrogel. The analysis from UV-Vis and TEM confirmed that the magnetic nanoparticles had good dispersion and stability in water under the condition of PCL- PEG-PCL with a particle size of 10-18 nm. For the resultant magnetically supramolecular hydrogel, its formation kinetics and mechanical strength could be affected by the concentration ofα-CD or PCL- PEG-PCL concentration and the content of incorporated iron oxide nanoparticles. It was found that with the increase ofα-CD or PCL- PEG-PCL concentration, the gelation time decreased and the hydrogel strength increased. The incorporated magnetic particles also speed up the gelation process and enhanced the hydrogel strength. From the analysis of the magnetic characterization, the supramolecular hydrogel showed a superparamagnetic property. BSA was used as a model drug to explore the application of this hybrid hydrogel in magnetic-controlled drug release. The in vitro release experametns showed that the BSA released slower from the hydrogel under the magnetic field condition.(2) Based on the strategy of multi-functional polymers, the hybrid hydrogel incorporated with Ag nanopartilces was prepared by using the amphiphilic copolymer Pluronic F-68 (PEO-PPO-PEO). Firstly, the F-68 was used to reduce the AgNO3 and disperse the resultant Ag nanoparticles in aqueous solution, and then mixed with an aqueous solution ofα-CD to form the hybrid hydrogel. From UV-Vis and TEM characterizations, it was found that Ag nanoparticles showed good dispersion stability in aqueous solution with a particle size of 5-7 nm. The rheology analysis was used to study the effects of the incorporating Ag nanoparticles on the gelation process and hydrogel properties. It was found that the incorporating Ag nanoparticles make the gelation time increase and the hydrogel strength decrease. From the SEM pictures, the Ag nanoparticles were found to be dispersed well in the hydrogel matrix. It was found that such hybrid hydrogels had good catalysis and antibacterial properties, as confirmed by methylene blue and Escherichia coli tests.(3) To fabricate an electroactive hydrogel, the multi-walled carbon nanotubes (MWNTs) were firstly modified by MPEG and dispersed in water, and then mixed with theα-CD solution. The analysis from UV-Vis and TEM confirmed that the MPEG-modified MWNTs had good dispersion stability properties in water. From the rheology analysis, it was found that the amount of MWNTs could affect the rheological properties of the hydrogels. With the increase of MWNTs amount, the gelation time increased and the hydrogel strength enhanced. The hydrogel had the shear-thinning and thixotropic properties, and the increasing MWNTs amount could increase their shear viscosity and thixotropy. The horseradish peroxidase (HRP) was encapsulated into the hydrogel to prepare a biosensor for hydrogen peroxide. The circular dichroism showed that the HRP could keep a good secondary structure and have enhanced thermal stability. The obtained biosensor provided a fast amperometric response to hydrogen peroxide (within 6 s). This biosensor exhibited a linear response to hydrogen peroxide in the concentration range of 0.1-2.4×10-3 mol/L with a correlation coefficient of 0.999 and a detection limit of 4.0×10-7 mol/L. The MWNTs could increase the sensitivity of the biosensor obviously, of which the sensitivity containing 0.2% MWNTs was four times as the one without MWNTs.The main innovations are as follows:(1) For the first time, the hydrophobic drug was encapsulated in the form of guest molecule into the hydrophilic hydrogel by the host-guest interactions. The release behaviors and biological activity of the drug were also studied. (2) A bioactive supramolecular hydrogel was fabricated by the host-guest interactions between heparin-modified MPEG andα-CD. The application of this hydrogel for dual-drug delivery was studied. (3) A new supramolecular hydrogel as gene carrier was prepared by the host-guest interactions betweenα-CD and poly(L-lysine)-modified polymeric guest and its properties for gene loading, controlled release, delivery and transfection were studied. (4) The magnetic nanoparticles were incorporated into the supramolecular hydrogel by the dual-functional amphiphilic block copolymers. The effects of introduced magnetic nanoparticles on the physical properties of hydrogels and their properties for magnetic-controlled drug release were also studied. (5) By using Pluronic F-68 functioned as reducing agent, dispersant and guest molecule, the hybrid supramolecular hydrogel incorporated with Ag nanoparticles was obtained. The applications of such a supramolecular hydrogel in catalysis and antibacteria function were also explored. (6) For the first time, the biosensor was fabricated by encapsulating HRP into the MWNTs-hybried supramolecular hydrogel. The effects of incorporated MWNTs on the hydrogel properties were also studied.
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