Novel Microneedle Arrays For Insulin Transdermal Delivery

The purpose of this study was to fabricate novel solid microneedle arrays using hyaluronic acid which is naturally found in many tissues of the body and investigate its physical and other characteristics. Insulin was used as a model drug to examine the enhancement effect in transdermal delivery and evaluate the hypoglycemic effect and the pharmacokinetics in diabetic rats.Firstly, scanning electron microscopy was used to inspect completed microneedle arrays. According to JIS K 5600-5-4 standard, the hardness of hyaluronic acid microneedles was determined using pencil method and the water content of the products was also measured. As a result, two kinds of microneedle arrays were both uniform in size with sharp tips. The hardness was above 6H and the water content was 6.17%.Secondly, the microphotographys of the skin and microneedle arrays were employed to examine the insertion ability and solubility. In vivo electrical resistance (ER) and transepidermal water loss (TEWL) measurements were made to clarify the disruption and recovery of skin barrier. Primary irritation test was used to verify the safety in rat skin. It was found that two kinds of microneedle arrays uniformly pieced the stratum corneum. The microneedle arrays of 200μm in length targeted delivery to the epidermis and the top part of needles dissolved after used in rat skin for 90 minutes. While the ones of 800μm in length inserted deeply into the mid-dermis below and dissolved completely after left into the rat skin for 60 minutes. The% change in ER and TEWL indicated that microneedles disrupted the stratum corneum barrier to a much lower extent than tape stripping did. The longer needles showed the more influence on the skin barrier and the slower recovery rate. The results of primary irritation test showed that the 200μm microneedle arrays have no irritation and the 800μm ones have slight irritation. Moreover, erythema extinction phenomenon showed the high safety of the microneedles in one way.In addition, insulin was selected as a model drug. Drug content, releasing rate as well as stability were investigated in the present study. FD4which has similar molecular weight to insulin was used to examine the mechanism of drug release from microneedles. The remarkable enhancement effect was observed for the microneedle arrays compared to insulin solution in the in vitro permeation experiment.Finally, hypoglycemic effects and insulin delivery made by microneedle arrays were measured in diabetic rats. They were observed in good accordance. Larger drops in plasma glucose level (PGL) and larger plasma insulin concentrations were shown due to higher dose insulin contained in microneedle arrays. Compare with subcutaneous administration of the same dose insulin, microneedle arrays reduced PGL to a similar extent but showed superior sustained action.In summary, this paper fabricated a novel solid microneedle arrays using hyaluronic acid as basic material which had well characteristics. Hypoglycemic effects made by microneedle arrays containing insulin as model drug in diabetic rats were observed significantly, which suggests prospect in development.