Hydrogel-based microneedles for the delivery of catalase protein

Abstract

Transdermal microneedles (MNs) have emerged as a powerful new technique for medicine and drug delivery. MNs are highly bioavailable, biocompatible, and non-invasive drug delivery systems. Catalase is one of the antioxidant enzymes that decomposes hydrogen peroxide to overcome oxidative damage. Enzymatic proteins such as catalase have a great therapeutic potential; however, their application in vivo is limited until now. For example, when they are administered orally, therapeutic proteins are easily degraded by proteases such as pepsin. In general, MNs can create micron-size channels, overcome the stratum corneum barrier, and deliver therapeutic proteins efficiently. Here, we designed hydrogel-based MNs to deliver catalase protein efficiently. For the fabrication of hydrogel-based MNs, the first step was to produce a MN master mold by using a 3D printer. The second step was to generate a polydimethylsiloxane (PDMS) mold by the reverse micro-molding technique. Next, a hydrogel solution with polyvinyl alcohol (PVA) and chitosan was optimized to produce casted hydrogel MN embraced with good mechanical properties. Among the ratio of PVA to chitosan used in the MN fabrication, the 2:1 ratio (w/w) of PVA:chitosan was the optimized composition for attaining ideal morphology and mechanical strength. Catalase was subsequently loaded onto the hydrogel MNs, and it was successfully delivered into the pig ear through passive diffusion. A longer residence time until 1 h improved the delivery of catalase that kept enzymatic activity after the delivery. Protein delivery using MNs was also strongly enhanced by external stimulations such as ethanol or ultrasound, which was known to disrupt the stratum corneum. The global market for MNs as a drug delivery system is ready to expand, and numerous applications of hydrogel-based MNs are anticipated to deliver therapeutic proteins.

Keywords: 3D Printing; Catalase; Drug delivery; Hydrogels; Microneedles.