Preparation Of Sustained-release Microneedles And Study On Drug Diffusion Process

Novel hydrogel microneedles have the advantages of have the advantages of safely loading multiphase drugs,sustained release,and controlled release.It has great potential application in the field of microneedle transdermal drug delivery.In this paper,the optimization process of the cross-linked hyaluronic acid microneedle patch was studied,and the performance of the microneedle patch was evaluated.Firstly,to explore the diffusion process of the drug in the skin,a model of the solid microneedle pierced into the skin was established.Use COMSOL software to simulate the release process of Dexibuprofen in the skin.Establish single and array(2x2)microneedle penetration models to explore the diffusion effect of Dexibuprofen.At the same time,a solid polypropylene(PP)microneedle was used to pierce the isolated mouse skin,and the release curve of Dexibuprofen was determined by in vitro transdermal diffusion experiment.The results show that the release curve obtained in the experiment is similar to the release curve predicted by the simulation,indicating that the established model can predict the release process of the drug in the skin to a certain extent.Secondly,under alkaline conditions,hyaluronic acid was cross-linked with 1,4-butanediol diglycidyl ether(BDDE).The cross-linked hyaluronic acid microneedles(cHA-MN)were fabricated by micro-casting method,and the process has been optimized.To verify that the prepared microneedle patch can meet the requirements of use,its appearance,mechanical properties,in vitro insertion properties,and swelling properties were characterized.The results showed that the cHA-MN patch prepared by the optimal process has excellent mechanical properties,which allows it to be inserted into the skin smoothly,and the swelling function can also be realized.Finally,cHA-MN was used to load dexibuprofen.The pre-loading and post-loading methods were used for drug loading to prepare D-cHA-MN-Ⅰ and D-cHA-MN-Ⅱ.The performance evaluation of these two kinds of microneedle arrays shows that they have sufficient mechanical strength.The release performance was studied through in vitro transdermal diffusion experiments.The D-cHA-MN-Ⅰ patch released about 42%of the drug in the first 6 hours,then the release rate slowed down,and the final cumulative release was about 90%.The D-cHA-MN-Ⅱ patch releases about 32%of the drug in 0-6h,and the final cumulative release is about 75%.Therefore,by using the preloading method to manufacture drug-loaded cHA-MN,a sustained-release microneedle with better drug release effect can be manufactured more quickly.