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用于潜在口腔黏膜疫苗传递的 MCM-41 型硅纳米粒子的移动组成物的表面修饰。

Surface Modification of Mobile Composition of Matter (MCM)-41 Type Silica Nanoparticles for Potential Oral Mucosa Vaccine Delivery.

机构信息

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent, ME4 4TB, UK.

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Kent, ME4 4TB, UK.

出版信息

J Pharm Sci. 2020 Jul;109(7):2271-2283. doi: 10.1016/j.xphs.2020.03.021. Epub 2020 Mar 30.

Abstract

Development of mobile composition of matter (MCM)-41 silica nanoparticles faces challenges, e.g. surface charge properties, antigen loading efficiency, protecting from enzymes and harsh GIT environment and effective release at target mucosal site. We report the production and characterization of polymer and amine modified MCM-41 type silica nanoparticles for oral antigen delivery using ovalbumin (OVA) as model antigen. Nanoparticles were characterized by dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, circular dichroism (CD), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), mucin binding, stability in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and in vitro OVA release in SGF and SIF. Unmodified nanoparticles size of 146 nm increased to 175-321 nm after modification while modified particles remained intact for more than 3 h in SGF and 96 h in SIF (DLS and SEM). Mucin binding proved polyethylene glycol (PEG) and chitosan modified nanoparticles as potential candidates for oral mucosa delivery. Both showed highest OVA encapsulation at 67% and 73%, and sustained OVA release in SIF (96 h) at 65% and 64% respectively. BET results showed that nanopores were not blocked during surface modification. CD and SDS-PAGE showed that OVA conformational structure did not change after release from the nanoparticles.

摘要

MCM-41 硅纳米粒子的移动组成(MCM)的发展面临挑战,例如表面电荷特性、抗原负载效率、防止酶和恶劣的 GIT 环境以及在靶粘膜部位的有效释放。我们报告了使用卵清蛋白(OVA)作为模型抗原的聚合物和胺改性 MCM-41 型硅纳米粒子的生产和特性。通过动态光散射(DLS)、差示扫描量热法(DSC)、X 射线衍射(XRD)、扫描电子显微镜(SEM)、BET 分析、圆二色性(CD)、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)、粘蛋白结合、在模拟胃液(SGF)和模拟肠液(SIF)中的稳定性以及在 SGF 和 SIF 中的体外 OVA 释放来表征纳米粒子。未经修饰的纳米粒子的粒径为 146nm,修饰后增加到 175-321nm,而修饰后的颗粒在 SGF 中超过 3h,在 SIF 中超过 96h(DLS 和 SEM)保持完整。粘蛋白结合证明聚乙二醇(PEG)和壳聚糖修饰的纳米粒子是口服粘膜给药的潜在候选物。两者均显示出最高的 OVA 包封率为 67%和 73%,并在 SIF(96h)中分别以 65%和 64%的比例持续释放 OVA。BET 结果表明,在表面修饰过程中纳米孔没有被堵塞。CD 和 SDS-PAGE 表明,OVA 构象结构在从纳米粒子释放后没有改变。

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