Study On The Mechanism Of Polymer Microneedle Drug Delivery Based On Vibration Synergy

As an alternative to oral and subcutaneous drug delivery,polymer microneedle drug delivery system not only has the advantages of minimally invasive and efficient technology,but also expands the drug delivery pathway of macromolecular substances such as vaccines,hormones,polysaccharides and proteins.With the development of microneedle technology,the synergistic effect mechanism of microneedle drug delivery system and other drug penetration-promoting methods has increasingly become a research hotspot,especially the synergistic effect of mechanical vibration stimulation and microneedle system.Significantly enhance the drug permeation flux.Inspired by the principle of bionics of mosquito mouthparts,the application of mechanical vibration stimulation is beneficial to reduce the insertion resistance of the skin to needle-like objects,and the reciprocating puncture movement of microneedles under vibration can increase the drug penetration rate exponentially.At present,microneedle research is mainly focused on the improvement of needle material and structure,while the research on polymer microneedle drug delivery technology and its mechanism under the synergistic action of vibration has a broader development prospect.In this paper,the mechanism of transdermal delivery of polymer microneedle under the synergistic action of vibration was studied from two aspects of simulation and experiment.At the same time,a drug-loaded microneedle forming method based on freeze-drying process is proposed,which makes the microneedle system have multiple functions,such as mechanical vibration stimulation,microneedle penetration,drug delivery and so on.In this paper,the vibrating microneedle system is divided into two parts:transdermal and drug delivery,and the mechanism is studied respectively,and the technological process of freeze-drying forming drug-loaded microneedle is explored.The main research contents are as follows:1)the transdermal mechanism of microneedle under the synergistic action of vibration was studied.Based on the simulation ofANSYS display dynamics,the skin puncture process of microneedle under the synergistic action of vibration was simulated,and the dynamic response results of the interaction between microneedle and skin three-dimensional model were characterized by equivalent stress and total deformation cloud images.Combined with the biological tissue section technique,the skin of mice after vibration microneedle puncture was observed in the biological tissue information microscopic imaging system.To explore the influence mechanism of vibration frequency and microneedle height on the puncture of biological skin by polymer microneedle array.Under the condition of 100Hz,150Hz and 200Hz vibration,the higher the vibration frequency is,the greater the equivalent stress inside the skin is,and the more obvious the effect of microneedle piercing the skin is.2)the mechanism of microneedle administration under the synergistic action of vibration was explored.The coupling simulation analysis of the process of microneedle insulin drug delivery under vibration was carried out based on TransientStructural and FluidFlow(fluent)module.The equivalent force cloud chart was used to characterize the skin response under the influence of vibrating microneedle,and the vibration frequency was used as a simulated variable to analyze the effect of vibrating microneedle on insulin drug flux.Combined with the experiment of vibrating microneedle insulin delivery in vitro,the results showed that under the experimental conditions,the transdermal delivery efficiency of microneedle to insulin was positively correlated with the applied vibration frequency,and the 200Hz vibration frequency increased the insulin permeation flux to 3.14 times compared with the blank experimental group,which verified the feasibility and high efficiency of vibration synergistic microneedle system in delivering insulin drugs.3)A multi-purpose microneedle drug loading scheme based on freeze-drying process is proposed in this paper.After vacuum drying at-50℃ and 15Pa for 10 hours,the PVA solution was dried and attached to the microneedle array substrate.PVA was used as the drug loading matrix to maintain a spongy connection between the microneedle body and the microneedle body.The preparation of drug-loaded microneedle by freeze-drying process has both the portable property of soluble microneedle and the high strength advantage of insoluble microneedle,which promotes the practical process of microneedle drug delivery technology.