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有利于将植物药“apocynin”递送至 BALB/c 小鼠诱导的暴发性肝炎的操作:体外和体内评估。

Propitious maneuvering for delivery of the phytopharmaceutical "apocynin" to induced fulminant hepatitis in BALB/c mice: In vitro and in vivo assessments.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia 35516, Egypt.

Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia 35516, Egypt.

出版信息

Int J Pharm. 2022 Oct 15;626:122165. doi: 10.1016/j.ijpharm.2022.122165. Epub 2022 Sep 9.

Abstract

Apocynin (APO), a specific nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase, NOX) inhibitor, has recently emerged as a bioactive phytochemical with eminent anti-inflammatory and anti-oxidant activities. To our knowledge, no research has been conducted to fabricate a mucoadhesive nanostructured delivery system of APO that targets the liver. Accordingly, chitosan (CS) surface decorated polymeric nanoparticulate delivery system (PNDS) was victoriously fabricated by double emulsion-solvent evaporation method. Herein, a randomized full 3 factorial design was employed to assess the impact of the independently processing parameters (IPPs) namely; (poly(d,l-lactide-co-glycolide) (PLGA) amount (A)), (polyvinyl alcohol (PVA) concentration (B)), and (CS concentration (C)), on different dependently measured attributes (DMAs). The optimal APO-loaded chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (APO-loaded CS-coated PLGA NPs) formula (F19) would be extensively appraised through meticulous in vitro-in vivo studies. Crucially, the results revealed that oral pre-treatment with the optimal formula evoked a prodigious in vivo hepatoprotective efficacy against lipopolysaccharide (LPS)/D-(+)-galactosamine (D-GalN) induced fulminant hepatitis (FH) in BALB/c mice when compared with pure APO, uncoated F19, and plain NPs (P NPs) pretreated groups. In conclusion, APO-loaded CS-coated PLGA NPs could be considered as a promising oral mucoadhesive phytopharmaceutical PNDS to open new prospects for therapeutic intervention in inflammatory based liver diseases.

摘要

APO(apocynin)是一种特异性烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NADPH-oxidase,NOX)抑制剂,作为一种具有显著抗炎和抗氧化活性的生物活性植物化学物质,最近受到关注。据我们所知,目前还没有研究制造针对肝脏的 APO 黏膜粘附纳米结构给药系统。因此,通过双重乳液-溶剂蒸发法成功制备了壳聚糖(CS)表面修饰的聚合纳米颗粒给药系统(PNDS)。在此,采用完全随机三因子设计评估了独立处理参数(IPPs)的影响,即:(聚(D,L-乳酸-共-乙醇酸)(PLGA)量(A))、(聚乙烯醇(PVA)浓度(B))和(CS 浓度(C))对不同的依赖性测量属性(DMA)的影响。将对载 APO 的壳聚糖包裹的聚(D,L-乳酸-共-乙醇酸)纳米粒(APO-loaded CS-coated PLGA NPs)的最佳配方(F19)进行广泛评估,包括细致的体外-体内研究。重要的是,结果表明,与纯 APO、未包被的 F19 和普通 NPs(P NPs)预处理组相比,口服预先用最佳配方处理可显著提高 LPS/D-(+)-半乳糖胺(D-GalN)诱导的 BALB/c 小鼠暴发性肝炎(FH)的体内肝保护作用。总之,APO 载 CS 包裹的 PLGA NPs 可被认为是一种有前途的口服黏膜粘附植物药 PNDS,为炎症性肝病的治疗干预开辟新的前景。

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