Study On The Performance And Drug Release Of Hyaluronic Acid And Dextran Nanofiber Hydrogel

Hyaluronic acid and dextran are natural macromolecular materials with excellent biocompatibility and biodegradability.They are widely used in biomedical fields such as tissue engineering,wound dressings,and drug delivery.Because of its poor spinnability,hyaluronic acid is rarely used alone in electrospinning.In this paper,the electrospinning hyaluronic acid and modified hyaluronic acid were studied systematically.Dextran molecules contain a large number of hydrogen bonds,which are easy to bind to drug molecules,resulting in a large drug loading and better drug encapsulation,so they are often used as drug carriers.However,dextran is extremely soluble in water and is prone to burst drug release.In this subject,photocrosslinked dextran nanofibers and hydrogels with good water resistance were prepared to improve the burst drug release.The spinning parameters of hyaluronic acid were studied in the first part.Hyaluronic acid was modified by using methacrylate anhydride to introduce double bonds and its structure was characterized by FT-IR.The effects of different solution systems on the morphology of electrospun modified hyaluronic acid fibers were studied.The modified hyaluronic acid was severely entangled in the molecular chain.The binding ability of hyaluronic acid with the solvent decreased due to the reduction of carboxyl group,so it was difficult to stretch to form the fiber before the solvent was completely evaporated.When the modified hyaluronic acid(Mw: 90,000)with similar mass fraction of dextran was blended,the nanofibers with better morphology were obtained.In the second part,dextran was modified with methacrylic anhydride to introduce double bonds.The effects of photocrosslinking time on the swelling,loss and mechanical properties of fibers were studied.When the photocrosslinking time was 2 h,the dissolution rate of the photocrosslinked nanofiber membrane is 47% and the water resistance was enhanced.The fiber has good swelling performance and the swelling ratio was 138,which was conducive to drug release.The breaking strength of dextran nanofibers after photocrosslinking for two hours was 5.8 MPa,which was more than doubled compared with the breaking strength of dextran nanofibers of 2.7 MPa.The drug release study was carried out by loading 5-fluorouracil into nanofibers.The drug in the unmodified dextran fiber membrane completely releases within one hour and the burst release phenomenon was obvious.At 37 °C,the cumulative release amounts of the photocrosslinked dextran nanofibers with a drug loading of 1wt% and 2wt% were 45% and 51% within 1 h respectively.The cumulative release amount was 41% and 49% respectively within 1h at 25 °C.The photocrosslinked nanofibers swell in water to form a nanofiber hydrogel.The drug was slowly released during the swelling process of the fiber and continues to be released until 12 hours.The total drug release of photocrosslinked dextran nanofibers with 1wt% and 2wt% drug was 74% and 79% at 37 °C,and was 72% and 73% respectively at 25 °C.In the third part,the dextran hydrogels and the 5-fluorouracil-loaded dextran hydrogels were prepared.The effects of irradiation time and solution concentration on the morphology and water resistance of hydrogels were systematically studied.At 37 °C,the cumulative drug releases of the hydrogels with drug loadings of 1wt% and 2wt% were respectively 33% and 37% within 1h,and the cumulative release of the drug was 34% and 37% within 1h at 25 °C.When the hydrogel swells in water,the drug wrapped inside the hydrogel was released from the pores.This process slowed down the release rate of the drug and continued to release until 12 hours.At 37 °C,the total drug release of dextran hydrogels with a drug loading of 1wt% and 2wt% was 68% and 72% respectively,and the total drug release was 55 % and 64% at 25 °C.