Study On Melittin Dissolving Microneedle Patchs Against Rheumatoid Arthritis

Objective: To prepare a rat model of rheumatoid arthritis treated with melittin soluble microneedle patch using soluble microneedle patch as a drug delivery carrier.The microneedle evaluation was used to evaluate the performance of piercing the skin;the diffusion behavior of the drug after transdermal administration was examined by the simulation of the in vivo distribution of the fluorescent drug;the percutaneous administration of the inflammatory cells was tested by the skin healing test and the experiment of inhibiting the increase of inflammatory cells Drug safety;explore its antiinflammatory effect against rheumatoid arthritis through animal experiments.It is hoped to lay the foundation for the development of new arthritis treatment dosage forms and provide new ideas and strategies for the treatment of rheumatoid arthritis diseases.Methods: 1.A melittin soluble microneedle patch was prepared by a two-step drying method,and three alternative excipients were prescribed for research.Use optical microscope and scanning electron microscope to observe its appearance and morphology;establish a method for the determination of melittin in soluble microneedle patches,explore its stability in excipient solution and the content of melittin in microneedle patches;The rat skin puncture experiment explored the proportion of microneedle accessories.2.Obtain the auxiliary materials and configuration concentrations required for the preparation of microneedles by prescription screening,and perform surface regularity,drug loading,puncture performance,intradermal erosion,in vivo drugs on the soluble microneedle patches prepared by the optimal prescription.Comprehensive evaluation of diffusion and skin healing.3.Using SD rats as experimental objects,prepare adjuvant arthritis rat models.Taking melittin(Mel)as a therapeutic drug,observe the changes of relevant signs,joint swelling,bone loss in the legs,synovial treatment,and expression of related cytokines in AA rats in each experimental group.The purpose is to explore whether the application of melittin soluble microneedles has a good anti-inflammatory effect on AA,and to provide a basis for clinical application of melittin soluble microneedles.Results: 1.A two-step drying method was used to prepare the melittin soluble microneedle patch.The microneedle patch was arranged in a complete needle shape and the matrix was clear and regular.By comparing the stability of the drug and excipients,the appearance of the microneedles,the drug loading capacity,and the ratio of the excipients,the preparation of the microneedle prescription for this experiment was finally screened: the drug melittin(Mel)and the needle material hyaluronic acid(HA)Aqueous solution(concentration 300 mg / m L)constitutes the microneedle needle part,and polyvinylpyrrolidone(PVP K90)aqueous solution(concentration 330 mg / m L)is used as the base part.Isolated skin puncture results show that microneedles can pierce the skin of rats,and the naked skin can be seen clearly on the surface of the isolated skin,with neatly arranged pores.It shows that the soluble microneedle patch prepared in this experiment has good puncture performance and provides a channel for drug delivery.3.The evaluation results of soluble microneedles show that the melittin soluble microneedle patch prepared in this experiment has complete needle shape and neat arrangement,and the drug loading can reach the effective therapeutic amount for treating AA model rats.A clear pore size was formed in the leg of the rat,indicating that the microneedles have good puncture performance;the microneedle patch can be completely dissolved within 20 minutes after being administered to the leg of the rat,indicating that the microneedles have the ability to dissolve quickly;microneedle administration and subcutaneous injection Compared with medicine,the medicine can be enriched in the administration area for a longer time,and the drug is released more slowly,indicating that the microneedles can function for a longer time;the skin and pathological sections of the legs are observed 24 hours after the microneedle administration The formed pore diameter gradually decreases,indicating that the microneedles will not cause damage to the skin and the skin will gradually heal.MTT experiments show that the excipients for preparing microneedles have good biocompatibility with cells,and melittin also can Maintain good biological activity.4.The results of pharmacodynamic experiments of soluble microneedle patch in model rats showed that the soluble microneedle patch significantly reduced toe swelling in AA model rats,and improved the degree of bone damage and bone loss in AA model rats.Condition,and reduced the levels of serum TNF-α,IL-6 and IL-1β,and significantly reduced ankle injury.The experimental results show that the microneedle group can significantly alleviate the development of rheumatoid arthritis in AA model rats.Conclusion: The soluble microneedle patch prepared in this project has complete needle shape and neat matrix arrangement.It has good puncture performance and mechanical strength,and is more stable than microneedle release drugs in other routes of administration.Micro has a good anti-inflammatory effect on AA model rats.The development of this experiment will lay the foundation for the development of new arthritis treatment dosage forms,and provide new ideas and strategies for the treatment of rheumatoid arthritis diseases.