Multilayered Microneedles for Triphasic Controlled Delivery of Small Molecules And Proteins.

Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics and has more stable delivery outcomes. However, many of these therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier and to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid-liquid phase separation that protects unstable proteins. We designed a 3-layer microneedle for the controlled release of three different molecules. Through micromolding, microneedles are efficiently generated, that benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The triple layers in the microneedles release the cargos in a three-phase manner. The released protein maintains its structure well. Moreover, we can control layer thickness by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics thus promising use in a multi-drug therapy through a single treatment. This article is protected by copyright. All rights reserved.