Study On Preparation And Drug Loading Performance Of DNA Hydrogel

Deoxyribonucleic acid(DNA)is the most important biological macromolecule in living systems.It has the function of encoding,storing,and transmitting genetic information.As a natural material,DNA molecules are biosynthetic and renewable.The characteristics of adsorption and biocompatibility can be used as functional materials.Hydrogel is a hydrophilic polymer with a three-dimensional network structure that water was used as a dispersion medium.The advantages of hydrogel include high water content,large drug loading space,and good biocompatibility.In terms of drug delivery systems,It has a wide range of applications.At present,cancer is still one of the main lethal diseases in humans.During the course of drug treatment,most anti-cancer drug carrier materials often have serious toxic side effects on normal cells and tissues due to their non-specific cytotoxicity.DNA hydrogel has a water-swellable three-dimensional network of cross-linked DNA chains.As a form of drug carrier,it can effectively achieve controlled release of drugs.Compared with other dosage forms,DNA hydrogel,as a drug-carrying system for anticancer drugs,can play a role as a carrier material without rejection in the human body,greatly reduce the toxic and side effects of drugs,improve the bioavailability of drugs,It can retain the advantages of the original hydrogel in drug loading system.Therefore,the application of DNA hydrogel as a drug carrier in the research and development of new anti-tumor drug delivery systems has great research prospects.The main research work of this paper are as the following research based on the above theory:Chapter 1: Preparation of physical cross-linked DNA hydrogels and study of drug loading performance.In this chapter,salmon hydrolyzed DNA sodium salt is used as a raw material,is used to prepare a physical cross-linked DNA hydrogel.Investigate factors that can affect physical gel-forming,such as raw material dosage,reaction temperature,time,buffer type and others.Scanning electron microscope(SEM)was used to characterize the morphology of physical cross-linked DNA hydrogels.Research on the drug loading and in vitro release of DNA hydrogel.The results show that the prepared physical cross-linked DNA hydrogel has a three-dimensional pore structure and the drug loading is about 22 %.With the addition of DNase Ⅰ enzyme,the dosage of physical cross-linked DNA hydrogel loaded with doxorubicin hydrochloride is 48 %of the loaded amount.Physical cross-linked DNA hydrogel is used as carrier Amycin.The results showed it has a good sustained release effect and the drug release time is extended,which greatly prolongs the drug release time.Chapter 2: Preparation of chemically crosslinked DNA hydrogels and study of drug loading performance.In this chapter,the DNA hydrogel is prepared by chemical cross-linking method using salmon sperm DNA sodium salt as raw material and ethylene glycol diglycidyl ether as cross-linking agent.The effects of raw material dosage,crosslinking agent type and time,incubation temperature and time on the gelling properties of DNAhydrogels were investigated,and the morphology of chemically crosslinked DNA hydrogels was characterized by scanning electron microscopy(SEM).The conditions of gel forming were investigated,such as the performance of chemically cross-linked DNA hydrogels in terms of morphology,drug loading,in vitro release,etc.The results show that the prepared chemically cross-linked DNA hydrogel has a three-dimensional pore structure,and the drug loading is about 35 %.With the addition of DNase Ⅰ enzyme,the amount of drug released from the chemically cross-linked DNA hydrogel loaded with doxorubicin hydrochloride is more than 80 %of the loaded amount,and the drug release time is greatly prolonged.Chemically cross-linked DNA hydrogel is used as carrier Amycin.The results showed it has a good sustained release effect and the drug release time is extended,which greatly prolongs the drug release time.Chapter 3: Preparation of self-assembling DNA hydrogels and study on drug loading performance.In this chapter,according to the literature,four DNA chain groups are complement,and then they are self into a cross structure,which is used as a substrate.Deoxynucleoside triphosphate can be gradually added to the DNA molecule without using a template.At the 3’-OH end,a long-chain DNA product is obtained.Then use the principle of base pairing to anneal hybridize A-rich and T-rich long-chain DNA to obtain a self-assembled DNA hydrogel.Investigate the responsiveness of the enzymes of self-assembled DNA hydrogels,and explore the effect of self-assembled DNA hydrogels as drug carriers on the release of doxorubicin hydrochloride.The results show that the self-assembled DNA hydrogel can tightly lock the drug in the gel layer,and the release amount is very small under the buffer condition of PBS7.4.After adding DNase Ⅰ enzyme,the drug in the gel layer can be slowly released.After 12 h,the drug release reached its maximum value.The research in this chapter provides an idea for the application of self-assembled DNA nanostructures in drug delivery vehicles.Chapter 4: Preparation of polyvinyl alcohol-sodium alginate-chitosan hydrogel and its drug loading performance.In this chapter,sodium alginate(SA)and polyvinyl alcohol(PVA)are used as raw materials to prepare hydrogel spheres by drip infusion,and then the chitosan protective layer is assembled on the surface of the hydrogel spheres by the action of positive and negative charges.Explore the difference between the drug loading properties of DNA hydrogel and polyvinyl alcohol-sodium alginate-chitosan hydrogel.The results showed that the average drug encapsulation rate of polyvinyl alcohol-sodium alginate-chitosan hydrogel was 2.157%,and the cumulative drug release rate reached more than 80 % of the loading capacity.The prepared gel as a drug carrier has a certain sustained release effect on doxorubicin hydrochloride.Conclusion: The chemical cross-linked DNA hydrogel prepared by chemical cross-linking method using natural salmon sperm DNA as raw material is superior to the physical cross-linked DNA hydrogel in drug loading and drug release performance;hydrogel with polysaccharide as raw material Compared with it,it has better drug loading performance.For self-assembling DNA hydrogels,the amount of DNArequired for the preparation process is the least.The preparation process is more complicated than the DNA hydrogels prepared from natural DNA in Chapters 1 and 2,but it can be personalized according to the DNA sequence.Design,realize the functionalization of DNA hydrogels,and provide new ideas and reference value for the research and development of DNA nanostructures and targeted controllable pharmaceutical preparations.In this study,DNA hydrogels and self-assembled DNA hydrogels prepared with natural DNA as raw materials have good development prospects in the delivery of anti-cancer drugs.They are for the development of new anti-cancer drugs with good biocompatibility and low toxicity.The preparation provides a new way of thinking.