Food Science College, Northeast Agricultural University, Harbin, People's Republic of China.
Department of Pharmaceutical Engineering, School of Materials Science and Chemical Engineering, Key Laboratory of Green Chemical Engineering in Heilongjiang Province, Harbin University of Science and Technology, Harbin, People's Republic of China.
Int J Nanomedicine. 2021 Feb 24;16:1405-1422. doi: 10.2147/IJN.S291090. eCollection 2021.
Iridoid glycosides (IG) as the major active fraction of Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats.
We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model.
SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of and and the production of TNF-α, IL-17, IL-23 and PGE2.
We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.
作为 Lindl. 的主要活性成分，环烯醚萜苷（IG）已被证实具有抗炎作用，可治疗溃疡性结肠炎（UC）。然而，其目前的商业制剂由于生物利用度低，无法到达发炎的结肠而受到限制。为了克服这一限制，我们制备了具有双重功能的 IG 载药纳米粒（DFNPs），以增加 IG 在结肠中的驻留时间。我们在大鼠中评估了 DFNPs 对 DSS 诱导的结肠损伤的保护机制。
我们使用油包水乳液法制备了 DFNPs。PLGA 被选为缓释聚合物，ES100 和 EL30D-55 被选为 pH 响应聚合物。通过 SEM 和 DLS 技术测量 NPs 的形态和粒径分布。为了评估 DFNPs 的结肠靶向性，将 DiR 包裹到 NPs 中作为荧光探针。研究了 NPs 的荧光分布。在结肠炎模型中评价了 NPs 在胃肠道中的治疗潜力和体内转运情况。
SEM 图像和 zeta 数据表明成功制备了 DFNPs。该制剂表现出高载药量。药物释放结果表明，在模拟胃液（pH1.2）和模拟小肠液（pH6.8）中，DFNPs 在最初的 6 小时内释放不到 20%。在模拟结肠液（pH7.4）中，超过 84.7%的药物能够持续释放 24 小时以上。载有 DiR 的 NPs 在结肠中的积累明显更高，这表明由于 pH 和时变聚合物的功能化，DFNPs 具有有效的靶向作用。DFNPs 可通过降低 DAI、宏观评分、组织学损伤和细胞凋亡，显著改善结肠损伤。我们的结果还证明，DFNPs 的强效抗炎作用是通过降低 NADPH、 和 基因表达以及 TNF-α、IL-17、IL-23 和 PGE2 的产生来实现的。
我们证实 DFNPs 通过抑制炎症反应发挥保护作用，可开发为一种有潜力的结肠靶向系统。
