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海藻酸包覆壳聚糖核壳纳米粒经口递送依诺肝素:体外与体内评价。

Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin: in vitro and in vivo assessment.

机构信息

Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar (M.P.) 470003, India.

出版信息

Int J Pharm. 2013 Nov 1;456(1):31-40. doi: 10.1016/j.ijpharm.2013.08.037. Epub 2013 Aug 29.


DOI:10.1016/j.ijpharm.2013.08.037
PMID:23994363
Abstract

The objective of present research work was to develop alginate coated chitosan core shell nanoparticles (Alg-CS-NPs) for oral delivery of low molecular weight heparin, enoxaparin. Chitosan nanoparticles (CS-NPs) were synthesized by ionic gelation of chitosan using sodium tripolyphosphate. Core shell nanoparticles were prepared by coating CS-NPs with alginate solution under mild agitation. The Alg-CS-NPs were characterized for surface morphology, surface coating, particle size, polydispersity index, zeta potential, drug loading and entrapment efficiency using SEM, Zeta-sizer, FTIR and DSC techniques. Alginate coating increased the size of optimized chitosan nanoparticles from around 213 nm to about 335 nm as measured by dynamic light scattering in zeta sizer and further confirmed by SEM analysis. The performance of optimized enoxaparin loaded Alg-CS-NPs was evaluated by in vitro drug release studies, in vitro permeation study across intestinal epithelium, in vivo venous thrombosis model, particulate uptake by intestinal epithelium using fluorescence microscopy and pharmacokinetic studies in rats. Coating of alginate over the CS-NPs improved the release profile of enoxaparin from the nanoparticles for successful oral delivery. In vitro permeation studies elucidated that more than 75% enoxaparin permeated across the intestinal epithelium with Alg-CS-NPs. The Alg-CS-NPs significantly increased (p<0.05) the oral bioavailability of enoxaparin in comparison to plain enoxaparin solution as revealed by threefold increase in AUC of plasma drug concentration time curve and around 60% reduction in thrombus formation in rat venous thrombosis model. The core shell Alg-CS-NPs showed promising potential for oral delivery and significantly enhanced the in vivo oral absorption of enoxaparin.

摘要

本研究工作的目的是开发海藻酸钠包被壳聚糖核壳纳米粒(Alg-CS-NPs)用于低分子量肝素依诺肝素的口服给药。壳聚糖纳米粒(CS-NPs)是通过壳聚糖与三聚磷酸钠的离子凝胶化合成的。通过在温和搅拌下用海藻酸钠溶液包覆 CS-NPs 制备核壳纳米粒。使用 SEM、Zeta-sizer、FTIR 和 DSC 技术对 Alg-CS-NPs 的表面形态、表面涂层、粒径、多分散指数、Zeta 电位、载药量和包封效率进行了表征。海藻酸钠的包覆使优化的壳聚糖纳米粒的粒径从 Zeta-sizer 动态光散射测量的约 213nm 增加到约 335nm,并通过 SEM 分析进一步证实。通过体外药物释放研究、肠上皮细胞的体外渗透研究、体内静脉血栓形成模型、荧光显微镜观察肠上皮细胞的颗粒摄取和大鼠的药代动力学研究评估了优化的载有依诺肝素的 Alg-CS-NPs 的性能。Alg-CS-NPs 对 CS-NPs 的包覆改善了依诺肝素从纳米粒中的释放特性,从而实现了成功的口服给药。体外渗透研究表明,Alg-CS-NPs 使超过 75%的依诺肝素渗透穿过肠上皮细胞。与普通依诺肝素溶液相比,Alg-CS-NPs 显著增加(p<0.05)了依诺肝素的口服生物利用度,表现为血浆药物浓度时间曲线的 AUC 增加了三倍,并且在大鼠静脉血栓形成模型中血栓形成减少了约 60%。核壳 Alg-CS-NPs 显示出用于口服给药的有前途的潜力,并显著增强了依诺肝素的体内口服吸收。

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[8]
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[9]
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