3D-printed insulin/GOx-loaded ZIF-8 microneedles via hydrogen-bond-enhanced photopolymerization for transdermal drug delivery

In the frontier of drug delivery research, the amalgamation of nanotechnology with 3D printing presents a transformative avenue for patient-centric therapies. This study presents the development of insulin/GOx-loaded Zeolitic Imidazolate Framework-8 (ZIF-8) microneedles, utilizing the unique properties of Metal-Organic Frameworks (MOFs) and advanced 3D printing techniques to enhance transdermal drug delivery systems. A key innovation lies in the use of a Polymerizable Deep Eutectic Solvent (PDES)-based ink for digital light processing (DLP) 3D printing, enabling accelerated photopolymerization and precise fabrication of microneedles. The PDES formulation, consisting of Betaine, Methacrylic Acid (MAA), 2-Hydroxyethyl Methacrylate (HEMA), Polyethylene Glycol Diacrylate (PEGDA), and the photoinitiator trimethylolpropane triacrylate (T-POL), was specifically designed to exploit hydrogen bonding interactions, thereby enhancing polymerization efficiency and structural integrity. The insulin/GOx-loaded ZIF-8 microneedles demonstrated responsive and controlled drug release, with notable sensitivity to glucose and pH changes, making them particularly suitable for diabetic applications. In vitro and in vivo results confirmed the superior drug encapsulation, stability, and release kinetics of the microneedles, showcasing their potential for effective and sustained transdermal delivery of insulin. This work establishes a new paradigm in the synthesis of multifunctional microneedles through the integration of MOFs and PDES for DLP 3D printing. The findings highlight the capability of this approach to address current challenges in drug delivery, offering a scalable, biocompatible, and responsive platform for advanced therapeutic applications.