Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia 35516, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia 35516, Egypt.
Int J Pharm. 2022 Oct 15;626:122165. doi: 10.1016/j.ijpharm.2022.122165. Epub 2022 Sep 9.
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.
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。