Preparation And Study On The Antioxidant And Antibacterial Effects Of Gallic Acid Hydrogel Drug Delivery System

Gallic Acid（GA）is a natural weakly acidic polyphenolic compound widely found in gallnut,cornus officinalis,pomegranate,polygonum multiflorum,cornus officinalis and sumac.Gallic acid or gallic acid is also known gallic acid gallic acid.Gallic acid has antioxidant,antibacterial,anti-inflammatory,anti-cancer and anti-viral effects.It also has strong biological activities to protect the cardiovascular system and nervous system,and can be used for anti-hypertension,anti-myocardial infarction,anti-vascular calcification and anti-diabetes,liver fibrosis,anti-tumor,etc.Because of its beneficial properties,this compound is widely used in food,cosmetics and drugs.Due to the presence of hydroxyl groups in the structure,GA is unstable to light,heat and p H,especially under strong oxidation conditions,alkaline and neutral conditions,and degrades rapidly.When taken orally,gallic acid is first absorbed by the gastrointestinal tract and then distributed primarily in the kidneys,where it is metabolized by the liver and then excreted by the kidneys.GA can be converted into many derivatives after digestion and metabolism,and methylation,glucosidation and sulfation products are the main forms of its metabolism in vivo.Due to extensive metabolism and clearance,gallic acid has poor pharmacokinetic properties,less absorption,fast metabolism,high clearance rate,hindered pharmacological activity and low bioavailability,which severely limits its use in clinical Settings^[1].In order to overcome these limitations of GA and enhance its pharmacological effects,different preparation development strategies were adopted to achieve site-specific targeting,increase retention,stability,and simultaneous delivery of hydrophilic and hydrophobic drugs.Structural optimization or dosage form adjustment of GA was beneficial to improve its bioavailability,which was an effective method to overcome the pharmacokinetic limitations of gallic acid.Hydrogel has good biocompatibility,and the hydrogel drug delivery system is easy to control drug delivery,which can minimize the shortcomings of traditional drug delivery and optimize the therapeutic effect of drugs.The introduction of hydrogels can increase the lipophilicity and bioavailability of gallic acid,reduce its shortcomings of fast absorption and elimination and low bioavailability,so as to optimize its curative effect.In this study,a sustained release preparation which can effectively control drug release was prepared to enhance the stability of gallic acid and improve the bioavailability of gallic acid,so as to solve the problems of low solubility and low bioavailability,and the antibacterial and antioxidant effects of the preparation were studied,which laid a foundation for the clinical provision of new preparations.1.Preparation and evaluation of gallic acid hydrogel delivery systemChitosan-2-acrylamide-2-methyl propane sulfonic acid（CS-G-AMPs）hydrogels were prepared by free radical polymerization using natural polymers chitosan（CS）and 2-acrylamide-2-methyl propane sulfonic acid（AMPS）as substrate for the controlled delivery of gallic acid.And the prepared hydrogels were studied by FTIR,XRD,TGA,DSC,SEM,sol-gel analysis,dynamic swelling,porosity,biodegradation,in vitro drug release and kinetic modeling.The results were as follows:Fourier infrared spectroscopy（FTIR）confirmed the successful preparation and loading of gallic acid in the hydrogel network;Differential scanning calorimetry（DSC）and thermogravimetric analysis（TGA）confirmed the improvement of thermal stability of chitosan and AMPS crosslinking and polymerization.X-ray diffraction（XRD）results show that the crystallinity of the raw material is reduced,indicating that the cross-linking of reagents is strong,forming a new polymer network of hydrogels.Scanning electron microscopy（SEM）results show that hydrogels have rough,dense and porous surfaces,which is consistent with the high cohesion of hydrogels.The porosity study showed that the porosity（78.36%）and drug loading of hydrogel increased with the increase of CS and AMPS concentration,and decreased with the increase of ethylene glycol dimethyl methacrylate（EGDMA）concentration.Sol-gel analysis showed that the gel fraction increased with the increasing concentration of CS,AMPS and EGDMA.The biodegradation studies showed that the hydrogel components with different weight ratios had significant effects on the degradation.The higher the concentration of CS,the better the degradation effect was,and the degradation rate slowed down with the increase of AMPS and EGDMA content.Swelling study showed that the swelling rate of hydrogel at p H 1.2（19.93%）was higher than that at p H 7.4（15.65%）.In vitro drug release studies showed that the maximum release of gallic acid reached 85.27%when p H was 1.2 and 75.19%when p H was 7.4 by UV-visible spectrophotometer,indicating that the prepared hydrogel had good acid-base stability and reversibility.Zero-order,first-order,Higuchi and Korsmeyer-Peppas models were fitted to determine the optimal release kinetics model of each preparation.Compared with other kinetics models,the"r²"value of each component of hydrogel prepared by Korsmeyer-Peppas model was close to 1.It shows that this model is the best fitting model.The above results showed that the prepared CS-g-AMPS hydrogel had good drug loading performance,stable and controllable.This study can provide reference for the development of new drug delivery system of gallic acid hydrogel.2.Study on antibacterial and antioxidant effects of gallic acid hydrogelThe antioxidant and antibacterial properties of the prepared gallic acid hydrogel were studied.Firstly,the antioxidant activity of hydrogels was studied by DPPH and ABTS free radical scavenging experiments.The results showed that the inhibition rate of hydrogels on DPPH was 73%,and the inhibition rate of ABTS was 70%,indicating that the prepared hydrogels had significant antioxidant activity and were an effective antioxidant.Then,the antibacterial effect of hydrogel was studied using Gram-positive（Staphylococcus aureus and Escherichia coli）and Gram-negative（Pseudomonas aeruginosa）.The results showed that the antibacterial zone diameter of hydrogel against gram-positive Escherichia coli and Staphylococcus aureus was 21mm and 16 mm,respectively.The diameter of inhibition against gram-negative bacteria Pseudomonas aeruginosa was 13mm,indicating that the prepared hydrogel showed certain inhibition against gram-positive bacteria（Escherichia coli and Staphylococcus aureus）and Gram-negative bacteria（Pseudomonas aeruginosa）,and had better inhibitory effect against gram-positive bacteria.The above results indicated that the prepared CS-g-AMPS hydrogel had antioxidant and antibacterial activities,and could be used as an effective hydrogel delivery system.