Study On Insulin Delivery And Sustained-Release Properties Of Microneedle Subcutaneous Implants

With the aging of the human body and the influence of various bad habits for a long time,the risk of people’s suffering from diabetes is showing an increasing trend year by year.Insulin,as a specific drug for the treatment of various types of diabetes,has always been limited by the single administration method that is the subcutaneous injection.Long-term subcutaneous injections have brought huge physical and psychological pain to the patient,reduced the patient’s compliance,and caused the risk of infection of the skin at the injection site.The development of the transdermal drug delivery system has brought a new dawn to diabetic patients.As a brand new transdermal drug delivery method,microneedle has gradually attracted the attention of scientific researchers.Traditional microneedles are mostly administered in the form of microneedle patches.The presence of patches has reduced the penetration ability of the microneedles on uneven skin surfaces and may cause unnecessary skin irritation.In order to solve these problems,this paper used polyvinyl alcohol,a biocompatible polymer material,to develop a patchless microneedle subcutaneous implant that can be implanted under the skin with auxiliary implant equipment.Mechanical performance experiments and invitro skin penetration experiments proved that the microneedle subcutaneous implant has enough mechanical properties to be successfully implanted subcutaneously.Optical coherence tomography images also showed that the microneedle subcutaneous implant can be completely implanted into the subcutaneous tissue of rats without breaking.In addition,we proved that the drug can achieve high drug delivery efficiency within 6 hours using the Franz diffusion cell..Animal experiments showed that the implantation process will not cause irreversible damage to the skin of rats,and the pinholes caused by implantation can heal by themselves within 180 minutes.The insulin-loaded microneedle subcutaneous implant has a good ability to lower blood sugar and can maintain the blood sugar of rats at a relatively stable level.Compared with the traditional subcutaneous injection of insulin,the phenomenon of concentrated burst release of drugs administered by microneedle subcutaneous implants is improved.In order to further improve the mechanical properties of the microneedle subcutaneous implants prepared above and meet the requirement of long drug delivery cycle,we used sodium hyaluronate as the needle matrix material and ivermectin as the model drug,and introduced PLGA microspheres are introduced into the microneedle subcutaneous implant to prepare a microneedle subcutaneous implant with drug slow-release function.Mechanical performance experiments and in-vitro skin penetration experiments showed that the microneedle subcutaneous implant has stronger mechanical properties,with a higher success rate of skin penetration.The in vitro hemolysis test and cell viability test prove that the microneedle subcutaneous implant has good biocompatibility and will not have a serious adverse effect on cell viability.In vitro release experiments proved that microspheres are the key structure to control the drug release rate,reduce the drug release rate,extend the drug administration cycle,and significantly inhibit the initial burst release of the drug.The results of animal experiments proved that,compared with subcutaneous injection,microneedle subcutaneous implants can significantly reduce the initial burst of drug release and maintain the blood drug concentration at a relatively stable level.