Study On Forming And Swelling Slow-release Process Of Double-drug-loaded Controlled-release Microneedle Array For Wound Healing

Skin is the main barrier to protect the human body from external invasion,and also one of the most important lines of defense to maintain the balance of body fluids,electrolytes,and nutrients.Due to external reasons or some chronic diseases,the skin is inevitably damaged,which seriously endangers human physical and mental health.For skin wounds,wound dressings are mainly used as the main means of skin healing in clinic.However,this delivery method has great limitation due to its low administration efficiency and poor air permeability,and it cannot carry out controlled drug release.As a new technology,microneedle technology can deliver drugs efficiently,painlessly and minimally invasive,and the microneedle-loaded drugs for wound treatment has great market potential.In this paper,based on the principles of polymer materials science and rheology,a dual-drug-loaded controllable sustained-release microneedle array for wound healing was proposed,and the multi-component drug delivery mechanism,the controllable sustained-release process,the micro-forming process of the microneedle array,and the drug delivery efficiency in the microneedles were deeply studied.The main contents are as follows:(1)Based on the linear viscoelastic model,Fick’s law and the hygroscopic expansion effect,a tip-drug-loaded swelling microneedle transdermal drug delivery topology was developed.The swelling characteristics of the tip-drugloaded swelling microneedles in the skin and the drug diffusion behavior were predicted by simulation.A variety of models were used to conduct system simulation calculations on the force and displacement changes of the microneedles(MN)after the swelling microneedles penetrated the skin,the concentration distribution of drugs in the skin at different times,and the drug delivery efficiency,which would provide some guidance for the subsequent design and preparation of microneedles.(2)A novel effective and controllable sustained-release microneedle array was developed based on chitosan and polyvinyl alcohol.On the basis of exploring the influencing factors in the microneedle molding process,the optimal preparation process of sustained-release microneedles was obtained:the number of centrifugation was controlled at three times,the rotational speed was 4000 r/min,the centrifugation time was 15 min,and the drying temperature was controlled at 35℃.At the same time,a series of tests were performed on the microneedle array such as morphology,size,mechanical properties,dissolution and swelling properties.The experimental results showed that the controllable sustained-release microneedle patch had excellent mechanical properties and could successfully penetrate the skin of mice.In addition,by chan that proportion of the substrate,the microneedle array with the accurate and controllable sustained-release time is obtained,and the requirement of different patients on more drugs can be met.(3)Aiming at wound healing,a double drug-loaded layered microneedle array loaded with ascorbic acid and basic fibroblast growth factor was prepared,and the drugs were successfully encapsulated at the tips of microneedles,with good layered delivery effect.At the same time,in order to separate the needle tip from the substrate,a double drug-loaded bubble microneedle array was developed.Both kinds of microneedle arrays have good morphology and mechanical properties,and can effectively pierce the skin of mice.In addition,the results of in vitro drug release experiments show that the double drug-loaded layered microneedle array has excellent sustained-release performance,which can release at least 55.6% of drugs within 12 h and at least 92% of drugs after7 d,further verifying the effectiveness of the double drug-loaded sustainedrelease microneedles for wound healing.