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Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake
Applied Nanoscience Pub Date : 2020-07-17 , DOI: 10.1007/s13204-020-01510-y
Mahwash Mukhtar , Mahira Zesshan , Salman Khan , Gul Shahnaz , Saeed Ahmad Khan , Hafiz Shoaib Sarwar , Riffat Asim Pasha , Hussain Ali

Mannose receptors (MR) are highly over-expressed on macrophages in the inflammatory bowel disease (IBD) and can be targeted by developing mannose-anchored nano-carrier system. In this study, mannosylated chitosan (MC) polymer was synthesized because of its high affinity for mannose receptors. Afterward, MC nanoparticles (NPs) were fabricated encapsulating dexamethasone to target macrophages for attenuation of inflammation at initial stages. Further, NPs were coated with a pH-sensitive polymer to control the premature drug release in the stomach. NPs were optimized using a surface response quadratic model to study the impact of various process parameters. Optimized NPs were then characterized for size, morphology, zeta potential, surface chemistry, biocompatibility, and uptake by macrophages. The average particle size was found to be 380 ± 19.8 nm with an encapsulation efficiency of 78.1 ± 1.17%. pH-dependent drug release profile was obtained with an average release of 73.9 ± 5.24% over 72 h in simulated intestinal fluid (pH 7.4). Moreover, the NPs uptake by the macrophages supported the viability of macrophages with the NPs and did not show any adverse effects. Moreover, this study was supported by the uptake of NPs inside macrophages. Altogether, the data supported that MC NPs could serve as a potential anti-inflammatory therapeutic approach to target macrophages in IBD.



中文翻译:

pH敏感的甘露糖锚定的纳米车辆的制备和优化,作为巨噬细胞摄取的有前途的方法。

甘露糖受体(MR)在炎症性肠病(IBD)中的巨噬细胞上高度过量表达,并且可以通过开发甘露糖锚定的纳米载体系统来靶向。在这项研究中,合成了甘露糖基化的壳聚糖(MC)聚合物,因为它对甘露糖受体具有很高的亲和力。之后,制造MC纳米颗粒(NP),将地塞米松包封以靶向巨噬细胞,以减轻初始阶段的炎症。此外,NPs被pH敏感聚合物包裹,以控制药物在胃中的过早释放。使用表面响应二次模型优化NP,以研究各种工艺参数的影响。然后,针对大小,形态,ζ电势,表面化学,生物相容性和巨噬细胞摄取来表征优化的NP。发现平均粒径为380±19。8 nm,封装效率为78.1±1.17%。获得了pH依赖性药物释放曲线,在模拟肠液(pH 7.4)中,在72小时内平均释放73.9±5.24%。此外,巨噬细胞对NP的摄取支持了巨噬细胞与NP的生存力,并且没有显示出任何不利影响。此外,这项研究得到了巨噬细胞内NPs的摄取的支持。总之,数据支持MC NPs可以作为潜在的消炎性治疗方法来靶向IBD中的巨噬细胞。此外,这项研究得到了巨噬细胞内NPs的摄取的支持。总之,数据支持MC NPs可以作为潜在的消炎性治疗方法来靶向IBD中的巨噬细胞。此外,这项研究得到了巨噬细胞内NPs的摄取的支持。总之,数据支持MC NPs可以作为潜在的消炎性治疗方法来靶向IBD中的巨噬细胞。

更新日期:2020-07-17
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