pH-Sensitive Naproxen Delivery via ZIF and Kaolin@ZIF Nanocarriers in 3D-Printed PLA-Gelatin Hydrogels.

This study presents a pH-responsive drug delivery platform, created based on naproxen-loaded zeolitic imidazolate frameworks (ZIF) and kaolin-ZIF (Kao@ZIF) nanocarriers embedded in a 3D-printed polylactic acid (PLA) scaffold coated with a gelatin hydrogel. The PLA discs were designed as structural tissue models to simulate localized drug release. Kaolin (Kao), a basic mineral in the kaolin group that includes halloysite, was selected as a chemically stable and biocompatible adsorbent to enhance ZIF integrity and system reliability. To address the concerns about the safety and reproducibility of nanoscale materials in biomedical applications, structurally stable ZIF and Kao@ZIF nanocarriers were synthesized and characterized using FT-IR, SEM-EDS, and LC-M/MS, measuring drug loading efficiencies over 90% for ZIF and slightly higher for Kao@ZIF. In vitro release profiles showed strong pH sensitivity, with greater naproxen release at acidic pH (5.4) and more sustained release from Kao@ZIF. Cytotoxicity assays using L929 fibroblasts demonstrated improved biocompatibility, with cell viabilities of approximately 75% for ZIF-naproxen, 82% for Kao@ZIF-naproxen, and 90% for gelatin-coated PLA-Kao@ZIF scaffolds, for 24 h incubation. Incorporating kaolin-stabilized ZIF nanocarriers into 3D-printed biodegradable scaffolds offers a promising and safer approach for pH-sensitive, tissue-targeted drug delivery, while laying the groundwork for future studies involving halloysite-derived nanotubular systems.