Study Of The Preparation And Application Of Transdermal Drug Delivery System Containing Hyaluronic Acid

Transdermal drug delivery is a potential alternative to oral and injection which allows the drug enters the systemic circulation through the skin,and its administration has many advantages.In recent years,transdermal drug delivery systems designed and developed for their advantages have gradually attracted people's attention but the poor penetration of drugs in this mode of administration has limited their application.Recently,studies have shown that hyaluronic acid is expected to be a carrier for transdermal delivery of drugs.Based on this,this paper aims at the structural and properties of hyaluronic acid,on the one hand,a novel transdermal delivery system is formed by the combination of hyaluronic acid and liposome;on the other hand,a hyaluronic acid prodrug containing 5-aminolevulinic acid is prepared by coupling,and 5-aminolevulinic acid is delivered to the skin by transdermal administration for photodynamic therapy of squamous cell carcinoma of the skin.The specific research content is mainly divided into the following two aspects: 1.Hyaluronic acid-containing ethosomes as a potential carrier for transdermal drug deliveryAs a transdermal penetration enhancer,ethosomes have a good penetrationpromoting effect and also have excellent biocompatibility,but poor stability limits their use.A hyaluronic acid-containing ethosomes(HA-ES)as the transdermal drug delivery system was prepared in this work,and rhodamine B(RB)was used as a model drug to be encapsulated.The obtained HA-ES-RB was then characterized by the surface morphology,entrapment efficiency,drug loading and the stability.Results showed that the prepared HA-ES-RB was spherical and showed good dispersion as well as the stability,with a particle size of below 100 nm.The skin permeation experiments were carried out in vitro with the Franz diffusion cells and the rat dorsal skins were used.It was found that the penetration effect of HA-ES-RB was much better than that of ES-RB.The fluorescence microscopy image showed that HA-ES-RB penetrated into the deepest dermis.The excellent transdermic drug delivery effect of HA-ES-RB maybe attributed from its smaller size,hydration of hyaluronic acid as well as greater potential targeting to skin and skin appendages of liposomal carriers.Moreover,the HA-ES delivery system showed non-cytotoxicity to normal cells,indicating a good biocompatibility.This work provded a hyaluronic acid-containing ethosomes which can offer a quick,high efficient,safe and self-administered transdermal drug delivery system.2.Transdermal pharmaceutical preparation of hyaluronic acid grafted 5-aminolevulinic acid for photodynamic therapy of squamous cell carcinoma of the skinPhotodynamic therapy(PDT)therapy based on 5-aminolevulinic acid(ALA)has become an effective method for the treatment of skin tumors.However,a major limitation of this therapy is the limited ability of hydrophilic ALA molecules to cross the stratum corneum of the skin.Therefore,we use hyaluronic acid as a penetration enhancer for transdermal absorption to improve the penetration of ALA.First,we prepared a hyaluronic acid grafted ALA by reaction,and characterized its chemical structure and its drug loading by infrared spectroscopy,nuclear magnetic resonance spectroscopy and elemental analysis,and the results showed that hyaluronic acid was successfully grafted with ALA and its drug loading could be as high as 27.22%.Secondly,the in vitro simulated transdermal diffusion experiments with the Franz diffusion cell showed that the hyaluronic acid grafted 5-aminolevulinic acid had a significantly better transdermal delivery effect than the free ALA solution.Subsequently,the inhibitory effect of hyaluronic acid grafted 5-aminolevulinic acid on skin squamous cell carcinoma A-431 cells was investigated.It was confirmed that HA-ALA has the same mechanism of action as ALA By measuring the concentration of PpIX and the level of ROS in A-431 cells.They are all converted to PpIX in cells and then cause an increase in ROS levels after illumination.In addition,cell viability assays and apoptosis assays after photodynamic therapy have shown that both HA-ALA and ALA can reduce cell viability by causing cell necrosis.This research work shows that hyaluronic acid grafted 5-aminolevulinic acid can not only improve the amount of drug penetration into the skin through the skin surface,but also exert its photodynamic efficacy,thus becoming an effective photodynamic therapy prodrug.