College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.
Research Institute for Drug Development, Pusan National University, Busan, 46241, Republic of Korea.
Arch Pharm Res. 2023 Jul;46(7):646-658. doi: 10.1007/s12272-023-01456-z. Epub 2023 Aug 3.
Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.
包含纳米粒和微球的结肠靶向口服给药系统已成为治疗溃疡性结肠炎（UC）的有前途的工具，因为它们可以最大限度地减少副作用并使局部药物浓度最大化。磷酸地塞米松钠（DSP）是一种有效的抗炎糖皮质激素，用于治疗 UC。然而，由于其副作用，它仍然是一种相当短期的治疗选择。在本研究中，我们开发了包封离子桥接 DSP-锌-聚（乳酸-共-乙醇酸）纳米复合物（DZP-NCs-in-microgel）的海藻酸钠凝胶，用于 UC 的口服局部治疗。通过 SEM 成像证实了 DSP-锌-PLGA 纳米复合物（DZP-NCs）成功包封在海藻酸钠微凝胶中。所制备的凝胶在刺激的肠液中释放 DZP-NCs，并抑制 DSP 在胃肠道上部的释放。此外，DZP-NCs-in-microgel 通过缓解临床症状和组织学标记减轻了葡聚糖硫酸钠诱导的结肠炎小鼠模型中的结肠炎症。我们的结果为治疗 UC 的地塞米松磷酸钠的口服结肠靶向递药提供了一种新方法。
