A solid polymer microneedle patch pretreatment enhances the permeation of drug molecules into the skin

Abstract

Solid microneedles (MNs) for skin pretreatment have attracted considerable attention in recent years due to their ability to increase skin permeability. There are several approved cosmetic products using microneedles in the market including Dermaroller, silicon MNs, etc. However, a safer MN which is made of biodegradable polymers hasn't been commercialized. Solid polymer MNs still need the support of theoretical data to realize the prospect of mass production and clinical application. In this work, we aim to employ polylactic acid (PLA) MNs to systemically investigate the mechanical and stability properties of the microneedles and the effect of MN dimensions, drug concentration, the viscosity of drug formulation and the administration time of drug on the skin on the drug permeation into the pretreated skin. Multiple applications test demonstrated MNs with the height of 600 μm possessed good mechanical stability performance. 800 μm depth microneedle and microneedle with the density of 256 MNs per cm² were most conductive to enhance the drug permeation. In addition, the increasing of drug concentration could increase the permeation amount of drug, but not affected on drug permeation rate. With the increase of drug viscosity, the drug permeation amount was decreased. To prolong the administration time of drug on the skin at 1 h, the drug permeation amount achieved a stable value and essentially unchanged after 1 h. Finally, the permeation effect induced by the MNs was demonstrated by insulin delivery in vivo. The blood glucose levels of diabetic mice were reduced to 29% of initial level at 5 h due to the increased permeability of insulin to the skin after MNs insertion. In conclusion, the biodegradable polymer solid microneedles can painlessly pierce the stratum corneum and accelerate the absorption of drug and active ingredients.