Study On Preparation And Characterization Of Environmentally Sensitive Hydrogels Composed Of Peptide-Based Polymer

Environmentally sensitive hydrogels have enormous potential in various applications. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. Development of environmentally sensitive hydrogels with excellent properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made. The work described in this thesis focuses on preparation, characterization, and application of environmentally sensitive hydrogels composed of peptide-based polymer.Polyaspartic acid (PAsp) hydrogels were synthesized by polysuccinimide (PSI), through chemical crosslinking using the crosslinking agent. Its environmental sensitivity was influenced by the synthesis condition, especially the terminal pH of hydrolyzation. High terminal pH enhanced the swelling/deswelling response rate and environment-sensitive properties, attributed to the number of carboxylate groups and the surface and porosity structure of dry gel. The swelling capacity of PAsp hydrogels showed high and special sensitivity to pH. Effect of H+/OH-concentration at various pHs led to several large changes of swelling capacity. The reversible pH-responsiveness resulted in wider applications for this intelligentized polymer.As far as we are concerned, the final goal for exploitation of a new material must be large-scale production, therefore, PAsp hydrogels must undergo this phase. The response surface methodology allowed a rapid screening of the important influence factors together with a polynomial model to optimize the preparation of PAsp hydrogels. The model predicted accurately the maximum point of the swelling ratio, and it showed a more than60%increase compared to the prior result.In addition, the preparation of PAsp hydrogels was modified by introducing some new method. First of all, employing the physical cyclic freeze/thawing technology and a small quantity of chemical crosslinker to synthesize it and improve its swelling capacity, under the precondition of maintaining its biodegradability and biocompatibility to result in a decrease in the toxicity of the chemical crosslinker. This novel super-absorber showed improved swelling behaviors over the one obtained only by chemical crosslinking as a result of the crystallization acting as the physical crosslink. To a certain extent, the final structures and properties can be controlled by regulating the freeze/thawing conditions. In order to remedy the poor mechanical strength of PAsp hydrogels, semi-IPN hydrogels composed of linear PAsp and cross-linked PAAc were prepared. The FTIR results proved the presence of a structure of polyelectrolyte complex in this hydrogel. The swelling phenomena of the semi-IPN products as a function of temperature and pH value of the medium, respectively, were investigated in detail, indicating that they kept the similar temperature-and pH-sensitivity with PAsp hydrogels. Furthermore, during the repeatable swelling and shrinkage period, the semi-IPN hydrogels showed suitable mechanical strength. Through investigating the dynamic swelling behavior of PAsp/PAAc semi-IPN hydrogels in urea solutions, it was found that the mechanism of the urea solutions diffusion into the hydrogels was non-Fickian. Moreover, to widen the application fields of our products, the influence of simulated biological fluids on the swelling phenomena was investigated. It was believed that our products would have wider applications, especially in biomedical fields for stimuli-responsive drug delivery systems.On the other hand, the second part of this dissertation investigated the formation of a new self-assembled hydrogel based on a short peptide RATEA16, which was formed under physiologically similar environment. The structural and physical properties were dependent on the environmental pH and concentration of peptide; the aggregation and formation of physical crosslinks that produce hydrogels were pH reversible. In such system, facial hydrophobic interaction, intermolecular hydrogen bond and a combination of attractive or repulsive electrostatic interactions were main causes for appearance of three phases (solution-hydrogel-precipitate) obtained in different pH environments. A delicate alteration of charge at the interface was significantly crucial for the pH-response. In addition, mechanical responsiveness was attributed to the self-assembled nature of the hydrogel scaffold, and the self-assembled hydrogels were able to recover from mechanical breakdowns.As its application study, insulin-FITC was used as guest proteins. The amphiphilic nature of peptide governs the pH responsiveness of the corresponding network, which makes it become an excellent candidate as pH-controlled drug release material. The loading/release process accompanying with the network formation/collapse, therefore, was reversible through changing the environmental pH, and the protein released from the delivery system returned its native structure. Significantly, it is promising that employing this peptide hydrogel in delivery applications. And it can also be shaped according to a vessel, suggesting that they are promising in tissue engineering and regeneration as responsive smart biomaterials.