Construction And Evaluation Of The System Of Composite Hydrogel As Drug Sustained And Controlled Release

As people’s requirements for medications continue to increase,the intelligentization of pharmaceutical dosage forms is constantly advancing,and hydrogels have been widely concerned by scientific researchers as a new intelligent drug delivery carrier.Hydrogel is a material with a three-dimensional network structure formed by polymers or monomers in various ways,and has been used in many frontier fields.The stimulus-responsive hydrogel can adjust its three-dimensional pore size to control the drug release,and can realize the active targeting of drugs.Its application research is also gradually developed in depth,and it is very promising to become an intelligent drug delivery system.Selective release of drugs at the lesion site for precise treatment is the general trend of drug delivery and disease treatment in the future.Oral administration is still the patient’s most tolerated and most convenient way of administration,but many drugs lose their activity due to unstable environmental factors such as p H and enzymes in the gastrointestinal tract.When the smart hydrogel is used as an oral drug delivery system,it can not only protect the biological activity of the drug,but also improve the drug delivery effect and bioavailability in the body,and enhance the therapeutic effect.A single polymer component or a single cross-linking hydrogel has poor performance and cannot meet application requirements.Because the network of this hydrogel is easy to disintegrate,the swelling time is short,and it is prone to burst and leakage;or its swelling is poor and the preparation reaction conditions are harsh,so it is prepared by a single polymer component or a single crosslink.The hydrogel is difficult to achieve the desired sustained and controlled release effect.Therefore,in order to improve the physical and chemical properties of this hydrogel and the physical and chemical properties of hydrogels,multi-component hybrid hydrogels have gradually entered the researcher’s field of vision.Nowadays,the application of hybrid multi-component hydrogels with multiple cross-linking methods has become a research hotspot.At the same time,the multi-layer hydrogel has the characteristics of multi-layer structure,relatively independent between layers and controllable number of layers.As a drug-loading system,it can highlight its structural advantages.However,most articles use the same or similar materials to prepare multi-layer structures,and there are few reports on the application of drug delivery systems.The preparation of composite multi-layer hydrogels with different gel layers from different materials and their application as drug-carrying systems deserves further investigation.In this paper,based on the advantages and disadvantages of the above-mentioned smart hydrogels and the development trend of its structure,different p H-responsive composite hydrogels are designed as slow and controlled release drug loading systems.The first chapter of this paper introduces the current classification and preparation methods of hydrogels,and at the same time briefly describes the research status of hydrogels in the fields of sustained and controlled drug release,tissue engineering and intelligent equipment,which proves that hydrogels have excellent development prospects and research significance;introduce the main polymer materials involved in this article,understand the physical and chemical properties of hydrogel preparation materials and application research in the field of medicine;then put forward the research basis,significance and content of this paper.The second chapter mainly introduces the excellent performance of p H-sensitive composite hydrogel prepared with sodium alginate(SA)and gelatin(Gel)as raw materials.Oxidized alginic acid(OSA)was used to chemically crosslink gelatin,and calcium chloride was used as the physical crosslinking agent of sodium alginate to prepare a composite hydrogel with low toxicity.Biological drugs have the disadvantages of instability,short half-life and low permeability in the human gastrointestinal tract environment,and the use of hydrogels as biological drug carriers is an effective way to overcome them.In this paper,the physical and chemical properties and morphological characteristics of SA/Gel composite hydrogels were analyzed by IR,XRD,and TGA.The newly prepared composite hydrogels were transparent three-dimensional network structures,and they also achieved physical and chemical double crosslinking.Because the preparation raw material has p H-sensitive groups,the formed composite hydrogel has good p H sensitivity.According to the characteristics of the composite hydrogel,the swelling rate of the SA/Gel composite hydrogel was measured under simulated gastrointestinal fluid conditions,and the release behavior and release mechanism of biomacromolecules in the system were explored.The results show that the swelling rate of the system can reach about 36 times;it has a significant sustained-release effect on the biomacromolecular drug bovine serum albumin(BSA)in vitro.Then,four classic drug release model equations are used to fit the drug release behavior.From the fitting results,it can be known that the release mechanism of the compound hydrogel in simulating gastrointestinal fluid is a skeleton-type diffusion mechanism.Chapter 3 mainly prepares a new double-layer p H-sensitive composite hydrogel sustained-release system based on natural polysaccharide materials and synthetic polymers,which has different internal/external hydrogel functions.The double-layer structure is made of different materials.The inner layer is SA and carboxymethyl cellulose(CMC),which is formed by mild physical cross-linking;the outer layer is formed by synthetic materials through chemical cross-linking by initiating polymerization,so the inner and outer Layers have different properties and can achieve their own unique functions.Fourier infrared spectroscopy,scanning electron microscopy and other methods are used to characterize the physicochemical structure of the hydrogel;swelling experiments are used to study the swelling properties of the double-layer hydrogel system;hydrophilic small molecule drugs,hydrophobic small molecule drugs and large molecules are used as a model drug,protein explores the drug release behavior of the system in simulated gastrointestinal fluids,and investigates the slow and controlled release effect of the system.Through the swelling experiment of the inner hydrogel,the material ratio to form the inner layer of the double-layer hydrogel is established.Finally,the mass ratio of SA:CMC is 1.0%:1.5% and 2.0%:0.5% to prepare the inner hydrogel;increase The preparation of the outer layer hydrogel can extend the swelling time of the hydrogel system from 4.5h to 12 h,indicating that the swelling performance of the double-layer hydrogel is significantly enhanced.The cumulative drug release experiment proves that the formation of the outer hydrogel can significantly prolong the drug release time,especially for BSA and hydrophobic drugs.The drug release behavior can be adjusted by changing the material types of the inner and outer layers and the thickness of the gel layer,indicating that the double-layer hydrogel is a programmable drug release system.Therefore,the double-layer hydrogel system can be developed into a new drug or bioactive substance sustained-release system,which has potential application prospects in new drug dosage forms.