Abstract
Microneedles (MNs) offer a minimally invasive approach for transdermal drug delivery, with dissolving MNs gaining popularity due to their biodegradability and controlled release properties. However, challenges such as air void formation in MNs, rigid base substrates and difficulties in multi-drug delivery limit their effectiveness. Here, we introduce a vacuum-assisted direct ink writing (DIW) method to fabricate high-strength, void-free, heterogeneous MN (hetero-MN) meshes. This approach enables precise control of drug composition and release kinetics within a single MN patch whose base substrate can be designed to have desired patterns and flexibility. We developed hetero-MN meshes with PLGA MNs for sustained release and HA MNs for rapid delivery, loaded with rhodamine B and fluorescein isothiocyanate-dextran as model drugs. The optimised MNs demonstrated reliable penetration in porcine skin, with HA MNs delivering drugs within an hour and PLGA MNs sustaining release over 40 days. Customisable hetero-MN designs highlight DIW printing as a promising platform for advanced multi-drug delivery applications.