Preparation Of Temperature/pH Dual Sensitive Hydrogels And Study On Their Drug Delivery Properties

Hydrogels are materials with three-dimensional networks formed by physical or chemical crosslinking of polymers that can absorb a large amount of water without destroying their structures,which have attracted considerable research attention in various fields such as food industry,drug carriers and tissue repair based on their good biocompatibility,degradability and soft tissue-like consistency.Intelligent hydrogels,which can render controlled drug release since they are capable of recognizing minute changes or stimuli in external environment that act on them,are increasingly used in drug delivery systems.Since some disease states manifest themselves by a change in temperature or pH value,temperature/pH sensitive hydrogels could be provided as ideal smart materials for development of new controlled drug delivery systems.However,many intelligent hydrogels are not high enough in mechanical strength and poor biocompatibility,which seriously limit their practical applications.Therefore,to prepare temperature/pH sensitive hydrogels with non-toxicity and high strength is of great significance for construction of drug delivery systems.In this paper,two kinds of temperature/pH sensitive hydrogels with good biocompatibility and satisfactory mechanical strength were prepared by radical polymerization,and their properties were also studied.The main contents were summarized as follows:1.A batch of temperature/pH sensitive hydrogels(PPA)with enhanced strength were prepared via free radical copolymerization and physical crosslinking without any crosslinkers with poly(ethylene glycol)methyl ether methacrylate(PEGMA)as temperature-sensitive monomer and acrylic acid(AA)as pH-sensitive monomer.Characterization of hydrogels was performed using Fourier transform infrared spectroscopy(FTIR),thermogravimetric analysis(TGA)and scanning electron microscopy(SEM).In addition,mechanical tests,swelling tests,in vitro release experiments and cytotoxicity tests were carried out.Mechanical tests showed that PPA hydrogels demonstrated high mechanical strength,and mechanical behaviors of resultant hydrogels were strongly affected by the content of AA.Experimental results of swelling tests indicated that hydrogels exhibited strong sensitivities towards pH,temperature and salinity.Furthermore,in vitro release experiments revealed that the amount of 5-Fu released from PPA hydrogels was relatively low in acidic condition(pH=1.2)but high in neutral environment(pH=7.4),and release rate was slower at 37? than that at 25?.Cytotoxicity tests showed that blank hydrogels were non-toxic,and hydrogels loaded with 5-Fu still maintained great cytotoxicity to cancer cells.All results above indicated that PPA hydrogels could be used as potential drug carriers for treatment of diseases such as colorectal cancer.2.Nanocomposite hydrogels(TCNCs/PHPA)with temperature/pH sensitivity,high strength and good biocompatibility were prepared by introducing hydroxypropyl methylcellulose(HPMC)and halocynthia roretzi tunicate cellulose nanocrystals(TCNCs)into PEGMA and AA systems.Characterizations were carried out using FTIR,TGA and SEM.And related properties such as mechanical strangth,swelling properties,drug release and cytotoxicity of hydrogels were investigated.Mechanical tests revealed that addition of TCNCs could increase the strength of hydrogels.In addition,TCNCs/PHPA hydrogels exhibited sensitivities to pH,temperature and salinity and displayed excellent compatibility with cells.In vitro release experiments indicated that TCNCs/PHPA hydrogels afforded high loading capacity for DOX,and their release behaviors were affected by gel composition,external temperature and pH.Release rate would be increased with decreasing of AA content,rising of temperature and reducing of pH value.Therefore,TCNCs/PHPA hydrogels could be used as drug carriers for controlled release of DOX.