Lidocaine plays a significant role in postoperative analgesia by effectively reducing pain. However, due to its short half-life, it is challenging for lidocaine to achieve the desired duration of analgesia in clinical settings. Drug delivery systems can regulate the release rate over time, making them one of the most effective strategies for achieving sustained release. In this work, a multi-level drug delivery system was designed using hyaluronic acid-modified zeolitic imidazolate framework-8 (HA/ZIF-8) nanoparticles and injectable hydrogels composed of modified natural polymers. Lidocaine was incorporating into the modified ZIF-8 and uniformly dispersed within the hydrogel network. The dynamic light scattering (DLS) and Fourier transform infrared spectrometer (FTIR) results indicate the successful loading of lidocaine into ZIF-8, while the X-ray diffractometer (XRD) results confirm that the loading of lidocaine did not disrupt the crystal structure of ZIF-8. The coating of hyaluronic acid on ZIF-8 enhanced cell biocompatibility, with cell viability increasing by 89% at the same concentration. This multi-level drug delivery system can be injected through a 27-guage needle. In vitro release studies demonstrated a sustained release of lidocaine for more than 4 days and kinetic simulations aligned with the Bshakar model, indicating its potential for use in long-acting analgesic preparations.
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