Preparation Of PH Intelligent Response Alginate/Gelatin For Drug Controlled Release Behavior Research

The drug controlled-release hydrogel carrier material developed with natural polymers as a matrix,due to good biocompatibility,degradability and non-toxicity,which has received extensive attention in the fields of bioengineering and medicine.Anionic alginate(ALG)and gelatin(GEL)are two important natural polymers that are cheap and available.Alginate can react with multivalent cations to form hydrogel,while gelatin has unique sol-gel characteristics,and the former also has good pH responsiveness.ALG can expand or contract at a specific pH,which is widely used in drug delivery research.However,a single alginic acid gel or gelatin has poor mechanical stability and is easy to swell after absorbing water,causing the drug released suddenly,which cannot achieve slow and controlled release of drugs.Therefore,in order to improve the mechanical stability,swelling and drug release properties of the gel,we intends to prepare several alginic acid/gelatin pH-responsive hydrogel microspheres through surface coating,interpenetrating network technology(IPN)and other methods to study its composition,structure,swelling and drug release behavior and drug release mechanism.The main research contents can be seen as follows:(1)Using the principle of in-situ gel,ALG@CMC series of hydrogel microspheres with a core-shell structure were prepared,in which the drug-loaded alginic acid gel microspheres as the core and carboxymethyl cellulose(CMC)in-situ gel as the shell,improving the mechanical stability of a single alginic acid gel and slow down the swelling and drug release rate of the gel microspheres.The thickness of the shell layer is controlled by controlling the content of Al3+.By using Scanning electron microscope(SEM)to observe the morphological characteristics of the microspheres,and using Fourier transform infrared spectroscopy(FTIR),thermogravimetric analysis(TG)and other means to characterize its composition and structure,and further study the swelling and drug release characteristics of the microspheres.The results show that this method successfully coats CMC on the surface of ALG microspheres,and controls the thickness of the CMC shell by controlling the content of Al3+.With the thickness of the CMC shell increases,the corresponding equilibrium swelling degree of the microspheres increases,the swelling and drug release rate gradually decrease,and its swelling and drug slow-release behavior have obvious pH response characteristics.(2)Using IPN technology,we plan to use alginic acid gel as the matrix material and carboxymethyl cellulose gel as the modifier to prepare a series of carboxymethyl cellulose and sodium alginate(ALG/CMC)fully interpenetrating networks(Full-IPN)Hydrogel,which can enhance the mechanical stability of a single alginic acid gel and slow down the swelling and drug release rate.The morphology of the microspheres was observed by SEM,and the composition of the prepared microsphere samples were characterized by methods such as FTIR and TG.The results show that the model drug(Indometacin,IDMC)is stably dispersed in the microspheres.As the Al3+cross-linking reaction time increases,the mechanical stability of the microspheres increases,the speed of swelling and drug release slows down.In addition,the composite microspheres still have obvious pH response characteristics.(3)Using in-situ ionic cross-linking method,sodium alginate is coated on the outer layer of GEL microspheres.The thickness of the shell layer is controlled by controlling the cross-linking reaction time and the ALG concentration.A series of ALG@GEL gel microspheres with a stable core-shell structure have been prepared,which not only enhance the mechanical stability of a single gelation gel,but also slow down the swelling and drug release rate of the microspheres.SEM FTIR,TG and other methods are used to characterize the morphology and composition of the prepared microsphere samples.The results show that the model drug is stably dispersed inside the microspheres.With the increase of Al3+ content and ALG gel concentration,the thickness of the shell layer increases.The shell layer effectively improves the stability of the gelatin microspheres and greatly slows down the swelling and drug release rate.In addition,the prepared microspheres still have obvious pH response characteristics.