Study On The Preparation And Application Of PH Sensitive Polyphosphazenes Hydrogels

At present, the main materials used for preparation of Glucose-sensitive hydrogels are polyamides and polyacrylates. However, these materials synthesized by monomer have a narrow adjustment in their physical and chemical properties. This could not meet the various demands in different drug release systems. Moreover, these materials lack satisfactory biodegradability and biocompatibility which are demanded when be put into the human body used for site-specific drug delivery. The limit to their use may be the low compliance related to the need of surgical implantation, which prompted us to develop new materials for drug release system. Recently, polyphosphazene has emerged as a new family of biodegradable polymers with an inorganic backbone consisting of alternating nitrogen and phosphorous atoms and two side groups attached to each phosphorous atom. All the inherent advantages including adjustable properties and degradation rate, satisfactory biocompatibility with human body and nontoxic degradation residues make poly(organophosphazenes) as promising biomaterial candidates.Up to now, the pH sensitive polyphosphazenes hydrogels usually contain carboxyl groups and response at alkaline medium. Little has been reported about polyphosphazenes hydrogels responded at acid medium. For this reason, a study was carried out regarding the synthesis of new polyphosphazenes more suitable for stimuli-sensitive hydrogels. The aim of this study was to prepare the pH sensitive hydrogels by introduce the alkaline groups to polyphosphazenes side group.Amino groups were attached to PDCP after protect by BOC2O, and then deprotected by HCl/HBr. By this method, a new series of polyphosphazenes have been synthesized. In this study, we found that BOC groups could be removed successfully via HCl/HBr treatment for 6 hours. And the degradation of the polyphosphazene backbone was observed during the deprotection.DGA and Allyl Alcohol co-substituted polyphosphazenes, DGA co-substituted polyphosphazenes, DGA and 2-methoxyethanol co-substituted polyphosphazenes, HEMA/DMAEA co-substituted polyphosphazenes, DMAEA and allylamine co-substituted polyphosphazenes, DMAEA and 2-methoxyethanol co-substituted polyphosphazenes, DMAEA and methoxyethoxy ethanol co-substituted polyphosphazenes, DGA and DMAEA co-substituted polyphosphazenes were firstly synthesized by nucleophilic substitution reaction. And they were characterized by 1H-NMR,IR and intrinsic viscosity. During the nucleophilic substitution reaction, it was found that the groups with low nucleophilic activity and large steric hindrance could hardly replace all the halogen. The remaining chlorine, which would lead to cross-linkage, should be replaced by the subsequent introduction of small molecular as cosubstituents. Hydrolysis of ester groups of HEMA occurred during the nucleophilic substitution reaction and post-processing. NaOH was used for adjusting the pH value to cancel the protonation of DMAEA after the substitution reaction.At last, synthesized polyphosphazenes were cross-linked to form hydrogels via different methods according their structural characteristic. The polyphosphazenes with amino group in the side groups were corss-linked by glutaraldehyde. It was found that DGA mono-substituted polyphosphazene with large amount amino groups was very brittle and hard to keep a certain shape after glutaraldehyde treatment. However, DGA and DMAEA co-substituted polyphosphazenes could form hydrogel with certain strength. Polyphosphazenes with HEMA or allylamine side groups could be cross-linked via free radical with AIBN at 65℃in the presence of HEMA Monomer. A new cross-link method for preparation hydrogel was studied via the residual P-Cl bond in polyphosphazenes. Furthermore, influences of swelling time, crosslinking degree, pH value, ionic strength and anion valence on the polyphosphazenes hydrogels behaviors were studied.An excellent biomedical material PAGP was prepared. And the preparation of PAGP microsphere was studied. In the experiment, double-emulsion systems were used for preparing the hollow microspheres. The main factors which affect the surface morphology, particle size and distribution of microspheres were the stirring rate of the solvent evaporation , surfactants based on the amount , the kind and amount of the emulsifier, curing time and curing temperature. The surface saponification of PAGP membrane was also investigated. NaOH concentration and reaction time were both effect on the surface hydrophilicity of membrane.All the polyphosphazenes hydrogels prepared in this paper are response in the acid medium, which can be changed to glucose-sensitive hydrogels after loading the glucose oxidase. The glucose sensitive hydrogels are response to the changement of glucose concentration and can be used as intellectual insulin delivery system.